Liquid extraction matrix assisted laser desorption ionisation ion source

Abstract

A Matrix Assisted Laser Desorption Ionization (MALDI) ion source is disclosed comprising a first device arranged and adapted to supply a flow of liquid on to the surface of a target or a sample to be analyzed so that the liquid forms a liquid junction on the surface of the target or the sample to be analyzed and wherein analyte molecules to be ionized are extracted into the liquid junction, and a laser source emits a laser beam which causes analyte ions or an analyte plume to be released or desorbed from the liquid junction.

Claims

1. A Matrix Assisted Laser Desorption Ionisation (MALDI) ion source comprising: a first device arranged and adapted to supply a flow of liquid on to the surface of a target or a sample to be analysed so that said liquid forms a liquid junction on the surface of said target or said sample to be analysed and wherein analyte molecules to be ionised are extracted into said liquid junction; and a laser source arranged and adapted to emit a laser beam, wherein said laser beam is arranged and adapted to cause analyte ions or an analyte plume to be released or desorbed from said liquid junction.

2. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said sample to be analysed is mounted or otherwise provided on said target.

3. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said target is at least partially formed from said sample to be analysed.

4. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said liquid is arranged to be supplied on to the surface of said target and/or said surface of said sample to be analysed.

5. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said flow of said liquid comprises a substantially continuous flow of said liquid.

6. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said liquid comprises one or more extraction solvents and/or one or more Matrix Assisted Laser Desorption Ionisation matrix substances.

7. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 6, wherein said one or more extraction solvents and/or said one or more Matrix Assisted Laser Desorption Ionisation matrix substances are arranged to draw out or extract one or more analytes from said target and/or said sample to be analysed.

8. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said laser beam is arranged and adapted to ionise said analyte molecules in said liquid junction.

9. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, further comprising a focusing device for focusing said laser beam to a focal point.

10. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 9, wherein said focal point is arranged so as to be located either upstream of said target, within said target, upon an upper surface of said target or sample to be analysed, at a location immediately adjacent an upper surface of said target or sample to be analysed or at a location downstream of an upper surface of said target or sample to be analysed.

11. A Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1, wherein said laser beam is arranged to impinge upon a rear surface of said target and to pass through said target so as to ionise analyte present in a liquid junction located on an upper surface of said target or said sample to be analysed.

12. A Matrix Assisted Laser Desorption Ionisation in source as claimed in claim 1, wherein said laser beam is arranged to impinge upon an upper surface of said target or said sample to be analysed, optionally without substantially being transmitted through said target, so as to ionise analyte present in a liquid junction located on an upper surface of said target or said sample to be analysed.

13. A mass spectrometer comprising a Matrix Assisted Laser Desorption Ionisation ion source as claimed in claim 1.

14. A mass spectrometer as claimed in claim 13, further comprising an Electrospray Ionisation ion source.

15. A mass spectrometer as claimed in claim 14, wherein said Electrospray Ionisation ion source is arranged and adapted to ionise or further ionise said analyte plume released from said liquid junction.

16. A method of ionising a sample comprising: providing a Matrix Assisted Laser Desorption Ionisation ion source; supplying a flow of liquid on to the surface of a target or a sample to be analysed so that said liquid forms a liquid junction on the surface of said target or said sample to be analysed and so that analyte molecules to be ionised are extracted into said liquid junction; and using a laser beam to cause analyte ions or an analyte plume to be released or desorbed from said liquid junction.

17. A method of mass spectrometry comprising a method as claimed in claim 16.

18. An interface for an ion source comprising: a first device arranged and adapted to supply a flow of liquid on to the surface of a target or sample to be analysed wherein said liquid is arranged to extract analyte molecules from said target or sample to be analysed so that a liquid junction comprising analyte molecules is formed on the surface of said target or sample to be analysed; and a second device arranged and adapted to desorb or release an analyte plume from said liquid junction, wherein said second device comprises a laser desorption device, an acoustic desorption device or a thermal desorption device.

19. An ion source comprising an interface as claimed in claim 18.

20. An ion source as claimed in claim 19, wherein said ion source comprises a corona discharge ion source, a glow discharge ion source, a surface collision ion source or an Electrospray Ionisation ion source and wherein said ion source is arranged and adapted to ionise or further ionise said analyte plume.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Various embodiments will now be described, by way of example only, and with reference to the accompanying drawing in which:

(2) FIG. 1 shows an embodiment wherein an extraction liquid is supplied on to the surface of a sample in order to extract analyte molecules from the sample into a liquid junction wherein the liquid junction is then ionised by a laser beam to form an analyte plume which is subsequently analysed by a mass spectrometer.

DETAILED DESCRIPTION

(3) An embodiment will now be described with reference to FIG. 1.

(4) FIG. 1 shows an embodiment wherein an ion source is provided comprising a sample 2 provided on a slide 1. The slide 1 may be transparent to laser radiation and laser radiation 6 from a laser (not shown) may be focused to a focal point which may be located immediately downstream of the sample 2.

(5) The slide 1 may be mounted on an x-y translation stage so that the slide 1 and associated sample 2 can be translated in both an x-direction and an orthogonal y-direction in order to enable ion imaging experiments to be performed wherein different portions of a sample are analysed and a mass spectral profile of the surface composition of the sample can be established.

(6) A capillary 3 or other flow device may be provided adjacent to the sample 2 and a liquid flow 4 of extraction solvent(s) and/or liquid Matrix Assisted Laser Desorption Ionisation matrix/matrices may be supplied via the capillary 3 or other flow device. Fluid or liquid may emerge from an exit of the capillary 3 or other flow device and may form a liquid junction 5 on at least a portion of the sample 2.

(7) A laser (not shown) may be arranged to generate a laser beam 6 which may be focussed by a lens 7 or other optical device to a focal point which according to the embodiment is arranged slightly downstream of the sample 2 and may be located in or within the liquid junction 5 which may be formed on the surface of the sample 2. However, other embodiments are contemplated wherein the focal point may be located at a different position e.g. upstream of the slide 1, within the slide 1, within or on the sample 2 or further downstream of the liquid junction 5.

(8) The extraction solvent(s) and/or liquid Matrix Assisted Laser Desorption Ionisation matrix/matrices which may be supplied via the capillary 3 or other flow device may cause analytes to be extracted from the sample 2 so that the liquid junction 5 may comprise analyte or analyte molecules which have been extracted from the sample 2.

(9) The laser beam 6 may be onwardly transmitted by the slide 1 which may be transparent, substantially transparent or semi-transparent to the laser radiation. According to an embodiment the slide 1 may transmit laser radiation without unduly attenuating the intensity of the laser radiation. According to an embodiment the slide 1 may be arranged to transmit at least 50%, 60%, 70%, 80% or 90% of the laser radiation received on the rear surface of the slide 1.

(10) The focusing of the laser beam 6 on to the liquid junction 5 may cause analyte ions 8 to be released or desorbed from the liquid junction 5 or an analyte plume to be released. The analyte ions 8 may then be directed towards an inlet device 9 of a mass spectrometer (not shown) or another ion source. According to an embodiment the inlet device 9 may comprise an inlet capillary or a nozzle-skimmer interface.

(11) The atmospheric pressure Matrix Assisted Laser Desorption Ionisation (AP-MALDI) ion source according to the embodiment is particularly advantageous compared to a conventional Matrix Assisted Laser Desorption Ionisation ion source (wherein a sample is provided in a vacuum chamber) since there is no requirement to put the sample inside a vacuum chamber.

(12) As a result, the ion source according to the embodiment described herein is less complex and less expensive compared with a conventional Matrix Assisted Laser Desorption Ionisation ion source.

(13) The atmospheric pressure ion source according to an embodiment also advantageously enables the analysis of samples to be performed which are potentially incompatible with vacuum conditions such as, for example, electrophoresis gels and polymer membranes which are prone to shrink when exposed to low pressures.

(14) The liquid atmospheric pressure Matrix Assisted Laser Desorption Ionisation ion source according to the embodiment enables multiply charged ions from proteins and peptides to be generated thereby allowing the analysis of relatively high molecular weight samples using a mass spectrometer having an atmospheric pressure ion inlet and/or wherein an ion inlet device of an atmospheric pressure mass spectrometer has an effective limitation on the mass to charge ratio transmission range of ions which may be transferred via the ion inlet device.

(15) Another embodiment relates to the use of Matrix Assisted Laser Desorption Ionisation as the ionisation technique instead of and/or in addition to an Electrospray Ionisation ion source wherein the Matrix Assisted Laser Desorption Ionisation ion source may be combined with liquid extraction surface analysis.

(16) The liquid extraction surface analysis liquid junction may be provided with a flow of extraction solvent(s) and/or liquid Matrix Assisted Laser Desorption Ionisation matrix/matrices wherein the total liquid flow rate into the junction may be substantially balanced by the ablation rate caused by the Matrix Assisted Laser Desorption Ionisation laser or other ionisation source.

(17) Although liquid extraction surface analysis has only modest imaging resolution compared with conventional Matrix Assisted Laser Desorption Ionisation techniques, according to an embodiment the ion source may be operated in various different modes of operation allowing a combination of techniques to be performed.

(18) According to an embodiment multiply charged Atmospheric Pressure Matrix Assisted Laser Desorption Ionisation surface imaging may be performed with liquid extraction surface analysis providing the liquid Matrix Assisted Laser Desorption Ionisation matrices resulting in analyte extraction.

(19) According to an alternative embodiment the laser beam may be arranged to impinge upon the target or sample to be analysed utilising a reflection geometry rather than a transmission geometry.

(20) According to an embodiment a laser may be used that assists in the extraction of sample from the surface for enhancing liquid extraction surface analysis devices. However, other embodiments are contemplated wherein desorption by other methods such as acoustic desorption and thermal desorption may be utilised.

(21) According to an embodiment the desorbed plume may not necessarily be immediately ionised or may only be partially ionised in which case the desorbed plume may then be ionised using a corona discharge ion source, a glow discharge ion source, a surface collision ion source or another type of ion source.

(22) Although a preferred embodiment of the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.