SAMPLE ANALYSIS

Abstract

A method of analysing a sample is disclosed in which a solvent emitting capillary is brought into contact with, or proximate to, a sample such that analyte from the sample is absorbed by solvent emitted from the capillary. A voltage is applied to the such that charged droplets of the solvent comprising the analyte from the sample are emitted from the capillary. The charged droplets are caused to be drawn into one or more sampling conduits connected to an atmospheric interface of an analytical instrument.

Claims

1. A method of analysing a sample, the method comprising: providing a capillary having an outlet at a first end; supplying a flow of solvent to the capillary such that solvent is emitted from the outlet of the capillary; bringing the sample and the first end of the capillary into contact with, or proximate to, each other such that analyte from the sample is absorbed by solvent emitted from the outlet of the capillary; applying a voltage to the solvent such that charged droplets of the solvent comprising the analyte from the sample are emitted from the first end of the capillary; and causing the charged droplets to be drawn into one or more sampling conduits connected to an atmospheric interface of an analytical instrument.

2. The method of claim 1, wherein the capillary is housed by a housing that forms a handle.

3. The method of claim 2, wherein the first end of the capillary is arranged at a distal end of the housing, and the one or more sampling conduits extend from the housing from a proximal end of the housing.

4. The method of claim 1, 2 or 3, comprising bringing the sample and the first end of the capillary into contact with, or proximate to, each other without applying the voltage, then separating the sample and the first end of the capillary, and then applying the voltage.

5. The method of any preceding claim, wherein the charged droplets are emitted from the first end of the capillary as a spray, and a nebulising gas is not used to form the spray.

6. The method of any preceding claim, wherein the charged droplets of the solvent comprising the analyte from the sample are emitted from the first end of the capillary and are then drawn into the one or more sampling conduits without impacting the sample.

7. The method of any preceding claim, wherein the one or more sampling conduits comprise one or more inlets, the first end of the capillary and/or the one or more inlets are moveable between a first position in which the one or more inlets are positioned away from the first end of the capillary, and a second position in which the one or more inlets are positioned downstream of the first end of the capillary, and wherein the method comprises: bringing the sample and the first end of the capillary into contact with, or proximate to, each other while the first end of the capillary and/or the one or more inlets are positioned in the first position; and wherein: causing the charged droplets to be drawn into the one or more sampling conduits comprises moving the first end of the capillary and/or the one or more inlets into the second position such that the charged droplets emitted from the first end of the capillary are drawn into the one or more sampling conduits through the one or more inlets.

8. The method of claim 7, wherein the capillary is housed by a housing, and is connected to the housing such that the first end of the capillary can move relative to the one or more inlets between the first and second positions, wherein in the first position the first end of the capillary extends out of the housing, and in the second position the first end of the capillary is arranged within the housing.

9. The method of claim 7, wherein the capillary is housed by a housing, and the one or more inlets are connected to a rotatable member that is rotatably connected to the housing such that the one or more inlets can move relative to the first end of the capillary between the first and second positions by rotating the rotatable member; wherein moving the first end of the capillary and/or the one or more inlets into the second position comprises rotating the rotatable member.

10. The method of claim 9, wherein the rotatable member forms a cover for the first end of the capillary when it is in the second position.

11. The method of any preceding claim, comprising causing evaporation of the charged droplets such that analyte ions are released, and wherein the analytical instrument analyses the analyte ions.

12. The method of claim 11, wherein causing evaporation of the charged droplets comprises heating the charged droplets.

13. The method of claim 11 or 12, comprising using the analysis of the analyte ions to classify the sample, optionally substantially in real time.

14. The method of claim 11, 12 or 13, wherein the analytical instrument is a mass spectrometer and/or an ion mobility spectrometer.

15. An apparatus for analysing a sample, the apparatus comprising: a capillary comprising a bore that runs centrally along a longitudinal axis of the capillary and forms an outlet at a first end of the capillary; a solvent supply line configured to supply a flow of solvent to the capillary such that solvent passes through the bore of the capillary and is emitted from the outlet of the capillary; a conductor configured to apply a voltage to solvent supplied to the capillary by the solvent supply line such that charged droplets of the solvent are emitted from the first end of the capillary; and one or more sampling conduits connectable to an atmospheric interface of an analytical instrument, wherein the one or more sampling conduits comprise one or more inlets, wherein the one or more inlets are moveable relative to the first end of the capillary and/or the first end of the capillary is moveable relative to the one or more inlets, and wherein the one or more inlets are configured to receive charged droplets emitted from the first end of the capillary when positioned downstream of the first end of the capillary.

16. The apparatus of claim 15, comprising a housing for the capillary, wherein the apparatus is handheld and the housing forms a handle.

17. The apparatus of claim 16, wherein the first end of the capillary is arranged at a distal end of the housing, and the solvent supply line and the one or more sampling conduits extend from the housing from a proximal end of the housing.

18. The apparatus of any one of claims 15 to 17, configured such that the charged droplets are emitted from the first end of the capillary as a spray by providing the solvent to the capillary and without the use of a nebulising gas.

19. The apparatus of any one of claims 15 to 18, comprising a housing for the capillary and a moveable member moveably connected to the housing, wherein the capillary and/or the one or more sampling conduits are connected to the moveable member such that the first end of the capillary and/or the one or more inlets can move between a first position in which the one or more inlets are positioned away from the first end of the capillary, and a second position in which the one or more inlets are positioned downstream of the first end of the capillary.

20. The apparatus of claim 19, configured such that in the first position the first end of the capillary extends out of the housing, and in the second position the first end of the capillary is arranged within the housing.

21. The apparatus of claim 19, wherein the moveable member is a rotatable member rotatably connected to the housing, and the one or more inlets are connected to the rotatable member such that the one or more inlets move relative to the first end of the capillary between the first and second positions when the rotatable member is rotated.

22. The apparatus of claim 21, wherein the rotatable member forms a cover for the first end of the capillary when in the second position.

23. The apparatus of any one of claims 15 to 22, further comprising a heater configured to heat charged droplets received by the one or more inlets.

24. The apparatus of any one of claims 15 to 23, wherein the apparatus is configured such that charged droplets received by the one or more inlets evaporate such that analyte ions are released, and wherein the analytical instrument is configured to analyse the released analyte ions.

25. The apparatus of claim 24, wherein the analytical instrument is a mass spectrometer and/or ion mobility spectrometer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0108] Various embodiments will now be described, by way of example only, and with reference to the accompanying drawings in which:

[0109] FIG. 1 shows a sample analysis apparatus in accordance with an embodiment;

[0110] FIG. 2 shows a sample analysis process in accordance with an embodiment;

[0111] FIG. 3 shows mass spectra obtained in accordance with an embodiment;

[0112] FIG. 4 illustrates real-time sample classification in accordance with an embodiment;

[0113] FIGS. 5A and 5B show a sample analysis apparatus in accordance with an embodiment; and

[0114] FIGS. 6A, 6B and 6C show a sample analysis apparatus in accordance with an embodiment.

DETAILED DESCRIPTION

[0115] FIG. 1 shows a sample analysis apparatus in accordance with an embodiment of the present invention. As shown in FIG. 1, the apparatus includes a solvent emitting device 101, a sampling assembly 102, and an analytical instrument 103.

[0116] The solvent emitting device 101 includes a capillary 114, to which a flow of solvent can be supplied. The solvent capillary 114 may be generally tubular, with solvent being supplied at one axial (solvent-receiving) (inlet) end, passing axially along a central bore, and being emitted at the opposite axial end, that is at an outlet or solvent-emitting tip 114A. The outlet (solvent-emitting tip) 114A of the capillary 114 may be tapered.

[0117] The solvent capillary 114 may be formed from any suitable material, such as fused silica and/or a metal, such as stainless steel, and/or a plastic, such as PEEK. In embodiments, the capillary 114 comprises fused silica with a plastic, e.g. PEEK, outer sheath. For example, the capillary 114 may be formed from PEEKsil? tubing. The inventors have found PEEKsil? tubing to be particularly robust.

[0118] The inner diameter of the capillary 114 may be between about 25 to 300 ?m. The outer diameter of the capillary 114 may be between about 0.5 and 2 mm.

[0119] A flow of liquid solvent may be provided to the inlet of the capillary 114 by solvent supply tubing 111. The solvent supply tubing 111 may be formed, for example, from PEEKsil? tubing. The solvent flow rate may be, for example, between about 5 and 15 ?L/min, such as 7 ?L/min or 10 ?L/min.

[0120] The flow of solvent may be user controllable. For example, the apparatus may include means for activating and deactivating the flow of solvent (now shown). The flow of solvent may therefore be stopped or reduced, e.g. during periods of inactivity, and initiated when required.

[0121] The solvent may comprise any solvent suitable for absorbing analyte from a sample. For example, the solvent may comprise an organic solvent such as acetonitrile. As another example, the solvent may comprise methanol. Other suitable solvents may include dichloromethane (optionally mixed with methanol), dichloroethane, tetrahydrofuran, ethanol, propanol, nitromethane, toluene (optionally mixed with methanol or acetonitrile), or water. The solvent may further comprise an acid such as formic or acetic acid. The solvent may further comprise one or more additives. In embodiments, the solvent comprises a liquid with an organic component, such as methanol water. For example, the solvent may include 98% methanol and 2% water.

[0122] A voltage may be applied to the device 101 in order to charge the solvent. For example, a voltage between about 0 and 5 kV may be applied to the capillary 114 or solvent in order to charge the solvent. In embodiments, voltages between about 3.5 and 5 kV may be applied to the capillary 114 or solvent. As shown in FIG. 1, a voltage for charging the solvent may be supplied via an electrical cable 112. The operating resistance may be about 10 MO.

[0123] The application of a voltage may be user controllable. For example, the apparatus may include means for activating and deactivating the voltage (not shown). The voltage may therefore be not applied or reduced, e.g. during periods of inactivity, and initiated when required.

[0124] As shown in FIG. 1, when a suitable voltage and flow of solvent are used, a spray of charged solvent droplets (electrospray) 115 may be formed at the solvent-emitting outlet or tip 114A of the solvent capillary 114.

[0125] The capillary 114 may be housed in a housing 113. The solvent capillary 114 and housing 113 may be arranged coaxially. The solvent emitting device 101 may be a handheld device. The housing 113 may accordingly form a handle to allow a user to manipulate the device 101 by hand, e.g. freely in three dimensions. The housing 113 may be formed of a suitable e.g. insulating material, such as a plastic.

[0126] The solvent supply tubing 111 and/or electrical cable 112 may be configured to allow the device 101 to be freely manipulated by a user in three dimensions. For example, the solvent supply tubing 111 and/or electrical cable 112 may be suitably flexible. The solvent emitting device 101 may thus be freely brought into contact with a sample that is desired to be analysed, e.g. in order to provide a point-and-click type analysis.

[0127] Furthermore, the solvent supply tubing 111 and electrical cable 112 may extend from the housing 113 from substantially the same location. For example, the solvent supply tubing 111 and electrical cable 112 may extend from an axial end of the housing 113 that is opposite to the outlet or solvent-emitting tip 114A.

[0128] Moreover, the solvent supply tubing 111 and electrical cable 112 may be mechanically linked to form a single flexible assembly. This can prevent tubing and cabling interfering with the sampling process, and thus increase user friendliness.

[0129] The solvent emitting device 101 may be configured such that when the solvent-emitting outlet or tip 114A of the solvent capillary 114 and a solid or liquid sample are brought into contact with (or sufficiently close to) each other (while a flow of solvent is being supplied to the capillary 114), liquid surrounding the solvent-emitting outlet or tip 114A becomes enriched with analyte molecules from the sample. When the solvent-emitting outlet or tip 114A and the sample are subsequently separated (and a voltage is supplied to the device 101), a spray of charged solvent droplets (electrospray) 115 may be formed at the solvent-emitting outlet or tip 114A of the solvent capillary 114, with droplets of the spray comprising (e.g. ionised) analyte from the sample.

[0130] To facilitate this, no nebulising gas may be supplied to the device 101, as the use of a nebulising gas may interfere with this analyte collection process. Moreover, the inventors have found that not using a nebulising gas can allow both solids and liquids to be sampled using the same apparatus configuration. Furthermore, not using a nebulising gas can simplify the device, and provide for more user friendly operation, e.g. as compared to using a nebulising gas to assist the formation of a spray of droplets.

[0131] Furthermore, the solvent-emitting outlet or tip 114A of the solvent capillary 114 may extend beyond the distal end of the housing 113, such that the housing 113 does not interfere with the analyte collection process. For example, the solvent capillary 114 may project beyond the distal end of the housing by a distance of at least 2 mm, 5 mm, or 10 mm. The solvent-emitting outlet or tip 114A of the solvent capillary 114 may thus provide a relatively small sample contact area.

[0132] The inventors have found that by providing a relatively small contact area at the tip 114A of the solvent emitting capillary 114, the amount of analyte material collected during contact with a sample can be relatively limited. This, together with the provision of a (e.g. continuous) flow of solvent, then means that following contact with the sample, substantially all, or most, of the collected analyte material can be emitted from the device 101 in a spray of charged droplets on a timescale of seconds, e.g. less than 1 s, 2 s, 3 s or 5 s. This means that a subsequent analysis can be performed using the device 101 within a few seconds of the previous analysis, with little or no signal carry over. A particularly convenient point-and-click type analysis can thus be provided.

[0133] The time taken for substantially all or most collected analyte material to be emitted from the device 101 may depend, for example, on the nature of the sample, and the nature of and flow rate of the solvent. In embodiments, the solvent composition and/or flow rate may therefore be adjustable by a user.

[0134] The probe device 101 may thus be used for both the extraction of molecules from the sample (solid surface or liquid), and the generation of an electrospray of sample containing droplets.

[0135] The sampling assembly 102 may include one or more sampling tubes 122 that each include an inlet 121 at one end and an outlet at the other end that is connectable to an atmospheric pressure inlet 131 of the analytical instrument 103.

[0136] When the sampling tubing 122 is connected to the atmospheric pressure inlet 131 of the analytical instrument 103 and a spray of charged droplets 115 emitted by the solvent emitting device 101 is directed towards an inlet 121 of the tubing 122, the droplets may be drawn into the inlet 121 and along the tubing 122, towards the atmospheric pressure interface 131 of the analytical instrument 103, e.g. due to gas flow caused by a vacuum of the analytical instrument 103. At least some of the solvent may evaporate as it passes through the tubing 122, such that analyte ions are released.

[0137] The tubing 122 may comprise one or more flexible regions, e.g. to accommodate movement of the inlet 121 relative to the analytical instrument 103.

[0138] The one or more flexible regions may be provided at any position along the tubing 122. Alternatively (substantially) the entire length of the tubing 122 may be flexible.

[0139] The tubing 122 may have a sufficient length to allow convenient operation remote from the analytical instrument 103. For example, the length of the tubing 122 may be at least 1 m, 2 m, 3 m or 4 m.

[0140] In embodiments, the sampling tubing 122 comprises a heated portion, or may be heated. This may facilitate desolvation of the analyte material, and thus increase sample signal.

[0141] The tubing 122 may be formed of an inert material, such as a plastic, such as Tygon?. The inventors have found that the use of an inert material can reduce signal losses, which may be caused, for example, by charged droplets and/or ions sticking to the tubing.

[0142] The analytical instrument 103 can be any suitable analytical instrument, such as a mass spectrometer and/or ion mobility spectrometer.

[0143] The atmospheric interface 131 of the analytical instrument 103 may be heated, e.g. up to a temperature of about 500? C. For example, the atmospheric interface 131 may comprise a heated capillary (not shown) through which droplets can pass. This may facilitate desolvation of the analyte material, and thus increase sample signal.

[0144] Analyte ions from the sample may thus be provided within a first vacuum chamber of the analytical instrument 103. The analytical instrument 103 may analyse the analyte ions to determine their mass to charge ratio and/or ion mobility, and/or to determine the mass to charge ratio and/or ion mobility of ions derived from the initial ions (for example by fragmenting the initial ions).

[0145] The analytical instrument 103 may include, or be in communication with, a processor configured to use the analysis to classify the sample. The classification may be performed substantially in real time.

[0146] FIG. 2 shows a method of analysing a sample according to an embodiment of the present invention.

[0147] At step 201, a flow of solvent is supplied to the solvent emitting device 101 via solvent supply tubing 111, such that solvent is emitted at the tip 114A of the capillary 114. The flow of solvent may be maintained (e.g. continuously) during at least the subsequent steps 202, 203 and 204 described below. A voltage may also optionally be applied to the solvent emitting device 101 via electrical cable 112 at step 201. In the case of a voltage being applied, the emitted solvent may be in the form of a spray of charged solvent droplets 115. In the case of a voltage not being applied, the emitted solvent may be an uncharged spray.

[0148] At step 202, a user brings the tip 114A of the capillary 114 and a sample 110 to be analysed into contact with each other (e.g. while solvent is (still) being emitted at the tip 114A of the capillary 114 due to the flow of solvent). For example, the user may move the handheld device 101 (by holding the handle) such that the tip 114A of the capillary 114 contacts the sample 110.

[0149] As shown in FIG. 2, the sample 110 may be a solid sample, in which case the tip 114A of the capillary 114 may touch the surface of the sample, or a liquid sample, in which case the tip 114A of the capillary 114 may dip into the liquid.

[0150] Alternatively, the tip 114A of the capillary 114 and the sample 110 may be brought sufficiently close to each other, but without actually physically touching, such that analyte material of the sample 110 collects with, and e.g. is dissolved by, solvent around the tip 114A of the capillary 114.

[0151] Where a voltage is applied to the solvent emitting device 101 at step 201, the voltage may continue to be applied during step 202, in which case the spray of charged solvent droplets 115 formed at step 201 may be disrupted by the contact or proximity between tip 114A and sample 110 at step 202. Alternatively, no voltage may be applied during step 202 (and optionally also not applied during step 201).

[0152] Not applying a voltage during the sample contact or proximity step (step 202) may be appropriate for analysis of living tissue, for example, e.g. in an intra-operative tissue analysis.

[0153] The user then separates the tip 114A of the capillary 114 and the sample 110 (by holding the handle) (e.g. while solvent is (still) being emitted at the tip 114A of the capillary 114 due to the flow of solvent).

[0154] As a result of the contact or proximity at step 202, solvent comprising absorbed analyte material of the sample 110 may collect around the tip 114A of the capillary 114, and/or (unabsorbed) analyte material of the sample 110 may collect around the tip 114A of the capillary 114 which is subsequently absorbed by solvent emitted from the tip 114A of the capillary 114. Thus, after the tip 114A and sample are separated, analyte material of the sample 110 may be present around the tip 114A of the capillary 114.

[0155] At step 203 (e.g. while solvent is (still) being emitted at the tip 114A of the capillary 114 due to the flow of solvent), a voltage is applied to the device 101 via electrical cable 112 such that a spray of charged solvent droplets 115 forms at the tip 114A of the capillary 114, with droplets of the spray comprising analyte of the sample 110 that collected around the tip 114A of the capillary 114 as a result of the contact or proximity at step 202. The application of the voltage may promote ionisation of analyte molecules.

[0156] The voltage may be applied (only) after the tip 114A and sample 110 have been separated. For example, the user may initiate the voltage application after separating the tip 114A and sample 110. Alternatively, where a voltage is applied to the solvent emitting device 101 at step 202 (and optionally also at step 201), the voltage may continue to be applied during step 203. That is, the voltage may be applied continuously.

[0157] At step 204, the spray of charged droplets 115 comprising analyte from the sample 110 is sampled by the sampling assembly 102. For example, the user may move the tip 114A of the capillary 114 into the vicinity of the inlet 121 of the tubing 122, and/or move the inlet 121 of the tubing 122 into the vicinity of the tip 114A of the capillary 114, such that at least some charged droplets emitted by the device 101 enter the inlet 121 of the tubing 122. For example, the tip 114A may be directed towards the inlet 121, with the distance between the tip 114A and the inlet 121 being, for example, less than 5 cm, less than 2 cm or less than 1 cm. Emitted charged droplets enter the inlet 121 without impacting the sample 110.

[0158] The voltage may be applied (only) after the tip 114A is in the vicinity of the inlet 121, or the voltage may be applied and then the tip 114A and inlet 121 may be brought into the vicinity of each other.

[0159] The solvent may evaporate as it travels towards the analytical instrument 103, e.g. in the tubing 122, and/or in the atmospheric interface 131 of the analytical instrument 103, to release analyte ions. The analyte ions may then be analysed by the analytical instrument 103. The analysis may be used to classify the sample.

[0160] The classification may be performed substantially in real time.

[0161] For example, a multivariate and/or library-based analysis may be used to classify the sample. For example, the analysis may comprise one or more of: (i) univariate analysis; (ii) multivariate analysis; (iii) principal component analysis (PCA); (iv) linear discriminant analysis (LDA); (v) maximum margin criteria (MMC); (vi) library-based analysis; (vii) soft independent modelling of class analogy (SIMCA); (viii) factor analysis (FA); (ix) recursive partitioning (decision trees); (x) random forests; (xi) independent component analysis (ICA); (xii) partial least squares discriminant analysis (PLS-DA); (xiii) orthogonal (partial least squares) projections to latent structures (OPLS); (xiv) OPLS discriminant analysis (OPLS-DA); (xv) support vector machines (SVM); (xvi) (artificial) neural networks; (xvii) multilayer perceptron; (xviii) radial basis function (RBF) networks; (xix) Bayesian analysis; (xx) cluster analysis; (xxi) a kernelized method; (xxii) subspace discriminant analysis; (xxiii) k-nearest neighbours (KNN); (xxiv) quadratic discriminant analysis (QDA); (xxv) probabilistic principal component Analysis (PPCA); (xxvi) non negative matrix factorisation; (xxvii) k-means factorisation; (xxviii) fuzzy c-means factorisation; and (xxix) discriminant analysis (DA).

[0162] The method may optionally include interrupting or stopping the supplied flow of solvent and/or applied voltage following the sample analysis, e.g. following step 204.

[0163] After a first sample analysis has been performed, a next sample analysis may then be performed. For example, the process may return to step 201 for the next sample (or portion of the same sample) to be analysed, and so on.

[0164] The method may optionally include cleaning the tip 114A of the capillary 114 following and/or before a sample analysis. For example, the tip 114A may be wiped, e.g. in between analyses of different samples or portions of the same sample. This may further reduce any signal carry over.

[0165] The inventors have found that embodiments of the present invention can provide a method of analysing a sample that is particularly convenient and simple, e.g. as compared to existing ambient ionisation techniques. For example, embodiments can allow direct sampling of both solid surfaces and liquids (or optionally gases) using a single apparatus configured in the same manner.

[0166] Furthermore, embodiments can provide a handheld analysis device which can be freely brought into contact with a sample remote from a mass and/or mobility spectrometer, e.g. in order to provide a point-and-click type analysis.

[0167] The inventors have found that the combination of direct and remote analysis coupled to real-time results of embodiments of the present invention may be particularly suitable for applications in clinical, pharmaceutical, forensic and airport security settings, amongst others.

[0168] FIG. 3 illustrates various analyses of various liquids and solid surfaces performed according to a method as described above. The mass spectra shown in FIG. 3 were each acquired by using the handheld solvent emitting device 101 to perform a single sample extraction, with a 2 m long flexible Tygon? tube, and a Waters Xevo? G2-XS QTof Quadrupole Time-of-Flight mass spectrometer. A solvent consisting of 98% methanol and 2% water was continuously supplied to the device 101 via solvent supply tubing 111 at a flow rate of 7 ?L/min, and a voltage of 5 kV was continuously applied via electrical cable 112.

[0169] As shown in FIG. 3, the technique is suitable for analysing both liquids and solid surfaces using the same apparatus configuration. For example, FIG. 3 show mass spectra obtained for liquids, including blood, milk, and sesame oil. The technique has also been used to analyse other liquids, including other oils and analytical standard solutions. FIG. 3 also shows mass spectra for solid surfaces, including pork muscle, aspirin and mouse brain section. The technique has been used to analyse other solid surfaces, including other flesh, biological tissue sections, bacterial colonies, pharmaceutical tablets and plastic objects. The technique has furthermore been found suitable for analysing nose swabs.

[0170] FIG. 4 shows another example analysis. In this example, a portable, single quadrupole mass spectrometer (Waters ACQUITY QDa Mass Detector) was used to obtain mass spectra. The mass spectra obtained were analysed using Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) (Waters LiveID software) in order to classify the sample substantially in real time.

[0171] Although in the above embodiments, the sampling tubing 122 is provided separate from the solvent emitting device 101, in other embodiments the sampling tubing 122 and solvent emitting device 101 are integrated into the same device. For example, FIG. 5 shows a handheld device 501 which includes both the sampling tubing and solvent supply built into the same device.

[0172] As shown in FIG. 5, in this embodiment, the sampling tubing 122 may extend from the housing 113 from substantially the same location as the solvent supply tubing 111. For example, the solvent supply tubing 111 and sampling tubing 122 may extend from an axial (proximal) end of the housing 113 that is opposite to the outlet or solvent-emitting tip 114A (at the distal end of the housing 113). Moreover, the solvent supply tubing 111 and sampling tubing 122 (and electrical cable 112 (not shown)) may be mechanically linked to form a single flexible assembly.

[0173] As shown in FIG. 5, the device 501 may be configured such that the inlet 121 to the sampling tubing 122 can move relative to the outlet or solvent-emitting tip 114A of the solvent capillary 114, for example between a first position in which the inlet 121 is remote from the outlet or solvent-emitting tip 114A of the solvent capillary 114 (e.g. as shown in FIG. 5A), and a second position in which the inlet 121 is arranged downstream of the outlet or solvent-emitting tip 114A (e.g. as shown in FIG. 5B). In the second position, the inlet 121 may be able to directly receive droplets emitted at the outlet or solvent-emitting tip 114A (e.g. without the droplets impacting the sample 510), whereas in the first position, the inlet 121 may be positioned to avoid interference with the outlet or solvent-emitting tip 114A being brought into contact with the sample 510.

[0174] For example, as shown in FIG. 5, the device 510 may include a rotatable member 521 that is rotatably connected to the housing 113 of the device, with the sampling tubing 122 connected to, and extending through, the rotatable member 521. The rotatable member 521 may be rotatable between a first position, e.g. as shown in FIG. 5A, in which the sampling tubing inlet end 121 and rotatable member 521 are remote from, and so do not interfere with, the outlet or solvent-emitting tip 114A, and a second position, e.g. as shown in FIG. 5B, in which the inlet 121 is arranged downstream of the outlet or solvent-emitting tip 114A so that it can receive droplets emitted at the outlet or solvent-emitting tip 114A.

[0175] In use, a user may bring the tip 114A of the capillary 114 and a sample 510 to be analysed into contact with each other (i.e. perform step 202 of the above process) while the inlet 121 (and rotatable member 521) is positioned in the first position. Sampling the spray of charged droplets comprising analyte from the sample 501 (i.e. step 204 of the above process) may then comprise moving the inlet 121 (and rotatable member 521) to the second position.

[0176] As can be seen in FIG. 5B, the rotatable member 521 may furthermore act as a cover for protecting the solvent-emitting tip 114A from damage, e.g. when the device 501 is not in use.

[0177] FIG. 6 shows another embodiment of a handheld device 601 in which both the sampling tubing and solvent supply are built into the same device. The embodiment shown in FIG. 6 includes a number of the features already described above, and only main differences with respect to the embodiment of FIG. 5 will now be described. It will be appreciated that FIG. 6A shows the device 601 with a half of the housing 113 removed for illustration purposes.

[0178] In contrast with the embodiment of FIG. 5 in which the inlet 121 to the sampling tubing 122 is moveable relative to the housing 113 and outlet or solvent-emitting tip 114A of the solvent capillary 114 (with the outlet or solvent-emitting tip 114A of the solvent capillary 114 being fixed in position relative to the housing 113), in the embodiment shown in FIGS. 6A-C the outlet or solvent-emitting tip 114A of the solvent capillary 114 is moveable relative to the housing 113 and inlet 121 to the sampling tubing 122 (with the inlet 121 to the sampling tubing 122 being fixed in position relative to (and within) the housing 113).

[0179] In particular, as shown in FIG. 6, the device 601 may be configured such that the solvent-emitting tip 114A of the solvent capillary 114 can move relative to the inlet 121 to the sampling tubing 122, for example between a first position in which the solvent-emitting tip 114A is remote from the inlet 121 (e.g. as shown in FIG. 6B), and a second position in which the solvent-emitting tip 114A is arranged proximate to and upstream of the inlet 121 (e.g. as shown in FIG. 6C). In the second position, the inlet 121 may be able to directly receive droplets 115 emitted at the solvent-emitting tip 114A (e.g. without the droplets 115 impacting the sample), whereas in the first position, the solvent-emitting tip 114A may be positioned such that it can be brought into contact with the sample.

[0180] For example, as shown in FIG. 6, the capillary 114 may be connected to a slidable member 621, and the housing 113 may include one or more complimentary features 622 configured to receive the slidable member 621, and through which the slidable member 621 can slide. The arrangement may be such that the solvent capillary 114 can slide axially between a first, extended position, e.g. as shown in FIG. 6B, in which the solvent-emitting tip 114A projects beyond a distal end of the housing 113, and a second, retracted position, e.g. as shown in FIG. 6C, in which the solvent-emitting tip 114A is arranged within the housing 114 and upstream of the inlet 121 so that the inlet 121 can receive droplets 115 emitted at the solvent-emitting tip 114A.

[0181] As illustrated in FIG. 6, the device 601 may be configured such that a voltage supplied by electrical cable 112 is applied to solvent to form an electrospray 115 when the capillary 114 is positioned in the second position (e.g. as shown in FIG. 6C), but is not applied to solvent when the capillary 114 is positioned in the first position (e.g. as shown in FIG. 6B).

[0182] In use, a user may bring the tip 114A of the capillary 114 and a sample to be analysed into contact with each other (i.e. perform step 202 of the above process) while the solvent capillary 114 is positioned in the first, extended position.

[0183] Sampling the spray of charged droplets comprising analyte from the sample (i.e. step 204 of the above process) may then comprise retracting the solvent capillary 114 to the second, retracted position.

[0184] As can be seen in FIG. 6C, in this embodiment, the housing 113 may act as a cover for protecting the solvent-emitting tip 114A from damage, e.g. when the device 601 is not in use.

[0185] The present invention may have particular application in food and environmental, surgical, at-line testing, transport security, illicit drug testing, and forensics contexts.

[0186] In embodiments, the device may be used intra-surgically, e.g. for cancer surgery applications. This may, for example, allow a surgeon to measure any suspicious tissue on the time scale of seconds, e.g. as compared to tens of minutes for other, e.g. frozen tissue section, approaches. Moreover, the present invention can a minimally invasive analysis, e.g. as compared to frozen section approaches where significant amounts of tissue may need to be removed. Accordingly, the present invention may facilitate a test everything approach, e.g. as compared to a test only what is practical approach. In embodiments, the method may be coupled to augmented visualisation, e.g. for providing surgical direction for complex procedures.

[0187] In embodiments, the sample is non-living. In embodiments where the sample from a human or animal body, the sample may be first removed from the body before analysis. In embodiments, the method is non-surgical and/or non-therapeutic and/or non-diagnostic.

[0188] Although 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.