Sample introduction system for spectrometers

Abstract

A method of mass or ion mobility spectrometry is disclosed that uses the Leidenfrost effect to cause a liquid to be repelled away from a heated surface so as to levitate above there-above. The repelled liquid is urged so as to move along the surface in a predetermined direction, for example, by the geometric configuration of the heated surface.

Claims

1. A method of mass or ion mobility spectrometry comprising: supplying liquid comprising an analyte towards a heated surface, wherein the heated surface is heated to a temperature that is sufficiently high to cause a portion of the liquid to vaporise and form vapour between the heated surface and the liquid; wherein the surface comprises a ratchet shaped profile such that the formation of said vapour repels said liquid away from the heated surface and focuses the analyte into an inlet aperture of a mass or ion mobility spectrometer; and wherein the method comprises urging the liquid along the heated surface and varying a force with which the liquid is urged along the surface so as to control a rate of movement of the liquid along the heated surface and thereby control a rate of evaporation of the liquid.

2. The method of claim 1 comprising urging the liquid along the surface using a gas flow, wherein the step of varying the force with which the liquid is urged along the surface comprises varying the gas flow so as to control the rate of movement of the liquid along the heated surface and thereby control the rate of evaporation of the liquid; or charging the liquid using an electric potential and urging the liquid along the surface using an electric field, wherein the step of varying the force with which the liquid is urged along the surface comprises varying the electric field so as to control the rate of movement of the liquid along the heated surface and thereby control the rate of evaporation of the liquid.

3. The method of claim 1, wherein the ratchet shaped profile is configured such that the formation of said vapour repels said liquid away from the heated surface and radially focuses the analyte into the inlet aperture.

4. The method of claim 1 comprising applying an electric potential to the ratchet shaped profile so as to charge droplets of the liquid; and applying an electric field to further focus the droplets into the inlet aperture.

5. The method of claim 1 wherein the ratchet shaped profile is arranged such that the formation of said vapour urges said liquid along the surface in a direction away from the inlet aperture; and the method comprises: providing a gas flow that urges the liquid towards the inlet aperture such that net force on the liquid causes it to move towards the inlet aperture; and/or charging the liquid using an electric potential and providing an electric field that urges the liquid towards the inlet aperture such that net force on the liquid causes it to move towards the inlet aperture.

6. The method of claim 1, further comprising subjecting the analyte to an ionisation technique in an ion source located downstream of the heated surface so as to form analyte ions.

7. The method of claim 1, wherein said liquid is provided to said heated surface in the form of liquid droplets.

8. The method of claim 1, wherein the liquid is transported through a tube and said heated surface forms at least part of the inside surface of the tube.

9. The method of claim 6, comprising using the heated surface to urge the liquid into the ion source of the mass or ion mobility spectrometer, ionising the analyte, and using the mass or ion mobility spectrometer to analyse resulting analyte ions.

10. The method of claim 1 wherein the ratchet shaped profile is configured such that the formation of said vapour urges said liquid along the heated surface towards the inlet aperture.

11. A mass spectrometer arranged and configured so as to perform the method of claim 1.

12. A method of mass or ion mobility spectrometry comprising: supplying liquid comprising an analyte towards a heated surface, wherein the heated surface is heated to a temperature that is sufficiently high to cause a portion of the liquid to vaporise and form vapour between the heated surface and the liquid; subjecting a sample to liquid chromatography in a liquid chromatography device; and supplying eluent from the liquid chromatography device as said liquid that is supplied towards the heated surface, wherein the surface comprises a ratchet shaped profile such that the formation of said vapour repels said liquid away from the heated surface and focuses the analyte into an inlet aperture of a mass or ion mobility spectrometer, and wherein the liquid is sprayed at said surface.

13. The method of claim 12, comprising directing a laser beam at the liquid in the ion source so as to form the analyte ions from the liquid.

14. The method of claim 12, wherein the heated surface comprises a substantially planar member having the ratchet shaped profile thereon and the inlet aperture therein, and wherein the liquid is moved along the substantially planar member and focused into the inlet aperture in the substantially planar member.

15. The method of claim 12, wherein the analyte is analysed by the mass or ion mobility spectrometer.

16. The method of claim 12, wherein the ratchet shaped profile is configured such that the formation of said vapour repels said liquid away from the heated surface and radially focuses the analyte into the inlet aperture.

17. The method of claim 12, further comprising: applying an electric potential to the ratchet shaped profile so as to charge droplets of the liquid; and applying an electric field to further focus the droplets into the inlet aperture.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

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

(2) FIG. 1 shows a liquid droplet being subjected to the Leidenfrost effect;

(3) FIG. 2 shows a preferred embodiment of the present invention in which liquid droplets are urged towards an inlet aperture of a mass spectrometer by the Leidenfrost effect;

(4) FIG. 3 shows a preferred embodiment of the present invention in which the Leidenfrost effect exerts a force on liquid droplets in a direction away from an inlet aperture of a mass spectrometer; and

(5) FIG. 4 shows a preferred embodiment of the present invention in which droplets are sprayed onto a plate that urges the droplets towards an inlet aperture of a mass spectrometer by virtue of the Leidenfrost effect.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENT

(6) FIG. 1 illustrates the principle of the Leidenfrost effect. The Leidenfrost effect occurs when a drop of liquid 2 is in near contact with a surface 4 that is hot enough to rapidly vapourise the liquid. The rapidly generated vapour forms a layer between the hot surface 4 and the drop of liquid 2 that causes the drop 2 to levitate above the hot surface 4. Typically, the drop 2 may be levitated 0.1 to 0.2 mm above the surface 4. This layer of vapour between the drop of liquid 2 and hot surface 4 has the effect of thermally insulating the drop 2 from the hot surface 4. The rate of evaporation of the drop 2 is therefore reduced, as compared to a drop in contact with the hot surface 4. Depending on the size of the drop of liquid 2, it can take several minutes to evaporate. By way of example, the Leidenfrost effect can be observed when drops of liquid are placed in a very hot saucepan and the drops are then seen to jump around the saucepan. In addition to liquids, the Leidenfrost effect can also be observed for sublimating solids.

(7) FIG. 2 shows a preferred embodiment of the present invention in which the Leidenfrost effect is used to drive liquid sample droplets 2 towards the inlet aperture 6 of a mass spectrometer. An inlet tube 8 is arranged upstream of the inlet aperture 6 for receiving the liquid sample 3. The inside of the inlet tube 8 is profiled so as to have a ratchet configuration 10 that includes a series of surfaces that are angled with respect to the longitudinal axis of the tube 8 and which face in a direction towards the inlet aperture 6. The tube 8 is heated to a temperate that is significantly hotter than the temperature at which the liquid sample 3 would boil at. The sample 3 is then injected into the inlet tube 8. As the sample droplets 2 moves towards or into contact with the angled surfaces 10 of the tube, a portion of droplet 2 rapidly vapourises, forming an expanding layer of vapour between the droplet 2 and the angled surface 10. This generates a force on the droplet 2 that propels the droplet 2 in a direction that is perpendicular to the angled surface 10. As the angled surface 10 faces towards the inlet aperture 6, the droplet 2 is propelled in a direction towards the inlet aperture 6. This process is repeated at each angled surface that the droplet 2 approaches on its path through the inlet tube 8, until the droplet 2 is fully vapourised. This technique can be used to desolvate an analyte in a liquid sample 3 containing analyte. This technique is also useful as it enables a liquid sample 3 to be introduced at a location that is remote from the inlet aperture 6.

(8) The sample 3 may be introduced into the inlet tube 8 by direct injection, or by infusion in another liquid or gas stream 12. For example, liquid chromatography eluent may be introduced into the inlet tube 8.

(9) FIG. 3 shows another embodiment that is the same as that shown in FIG. 2, except that the angled surfaces 10 on the inside of the inlet tube 8 face away from the inlet aperture 6 of the mass spectrometer. Also, the liquid sample introduced into the inlet tube 8 is eluent 14 from a liquid chromatography column. As the angled surfaces 10 on the inside of the inlet tube 8 face away from the inlet aperture 6, the Leidenfrost effect exerts a force of the droplets 2 in a direction away from the inlet aperture 6. Although the net force on the analyte causes the analyte to move towards the inlet aperture 6, the angled surfaces 10 slow the motion of the droplets 2 in the direction towards the inlet aperture 6.

(10) FIG. 4 shows a cross-sectional view of another embodiment comprising a sprayer 16 for spraying analyte solution droplets 2 and a plate 17 for directing the droplets 2 towards the inlet 6 of a mass spectrometer. The centre of the plate 17 comprises an aperture 18 that is connected to the inlet 6 of the mass spectrometer. The plate 17 is preferably planar and may be any shape such as, for example, circular, square or rectangular. The side of the plate 17 that the analyte is sprayed towards comprises a plurality of angled surfaces 10. Each of the angled surfaces 10 faces in a direction towards the aperture 18 in the plate 17. In operation the plate 17 is heated to a temperate significantly above the temperature that the liquid sample would boil at and sample droplets 2 are sprayed at the plate 17. As in the above embodiments, the heated surface 4 results in the Leidenfrost effect taking place. As the heated angled surfaces 10 are directed towards the aperture 18 in the plate 17, this has the effect that the droplets 2 are directed towards the aperture 18 in the plate 17 whilst they evaporate. The droplets then pass through the aperture 18 in the plate 17 and into the mass spectrometer inlet aperture 6.

(11) Although the plate 17 in this embodiment is depicted with an overall planar shape, it is also contemplated that the overall shape of the plate 17 may be such that droplets 2 are urged in the direction of the inlet aperture 6 under the force of gravity. For example, the overall shape of the plate may be funnel shaped so as to achieve this. Other means of providing a net force on the droplets 2 towards the inlet aperture 6 are also contemplated. For example, a gas flow may be provided that provides a net force on the droplets towards the inlet aperture.

(12) In all embodiments of the present invention, the heated angled surfaces 10 may be arranged such that the Leidenfrost effect generates a force that urges the droplets 2 towards the inlet aperture 6 so as to quicken the motion of the droplets 2 towards the inlet aperture 6. Alternatively, the angled surfaces 10 may be arranged such that the Leidenfrost effect generates a force that urges the droplets 2 away from the inlet aperture 6 so as to slow the motion of the droplets 2 towards the inlet aperture 6.

(13) By shaping the inner surface structure of the inlet tube 8 or the surface of the plate 17 with suitably designed angled surfaces 10, droplets 2 can be propelled in a net direction that is based on the angle of the surfaces 10. The angled surfaces 10 may be arranged and configured in different manners depending on the droplet size incident on the angled surfaces 10 and the solvent characteristics of the sample solution.

(14) The present invention may be used to introduce a sample to the mass spectrometer from a remote location. The present invention may be used to control the transit time and the desolvation rate of the droplets 2.

(15) The geometry of the angled surfaces 10 and/or the temperature of the heated surface 4 provide means for vapourising the liquid to the optimum droplet size for interaction with a surface or for ionisation techniques. For example, the present invention may be used to control the size of the droplets 2 for use in solvent assisted ionisation (SAI), an impactor ion source or rapid evaporation ionisation mass spectrometry (REIMS).

(16) The present invention also provides the advantage that cross-contamination of samples (carryover) may be reduced since the Leidenfrost effect means that each liquid sample does not directly contact the walls of the inlet tube 8 or plate 17.

(17) 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.

(18) For example, the angled surfaces 10 may be used to move multiple streams of liquid droplets 2 and may be used to urge the streams together so as to mix the droplets 2 from the multiple streams. Moving and mixing multiple liquid droplets streams together may be used to perform on-line chemistries in preparation for mass spectrometry. For example, a MALDI analyte droplet may be mixed with a MALDI matrix. Alternatively, trypsin may be mixed with a sample in order to perform fast digestion of the sample.

(19) The present invention may also be used to manoeuvre liquid droplets 2 to a desired location in a mass spectrometer. For example, the Leidenfrost technique may be used to deposit liquid droplets 2 onto defined regions of a sample plate in preparation for ionisation such as, for example, by MALDI or DESI type surface ionisation.

(20) An electric potential may be applied to the angled surfaces 10 so as to charge the droplets 2. An electric field may then be applied so as to manipulate the charged droplets 2, e.g. in order to focus the stream of droplets 2 and/or improve transmission of the droplet stream through the device.

(21) Using the Leidenfrost phenomena to levitate droplets 2 is advantageous in that the sample is not in direct contact with the walls of the containment vessel or sample plate. Wall-less sample preparation has advantages in that the sample cannot be contaminated or mixed with the remains of other samples. Conventional techniques are known for wall-less sample preparation, but these require complex AC and DC voltages to be applied.

(22) The angled surfaces 10 of the present invention may be hydrophobic surfaces, which may further enhance the repelling effect between the surfaces 10 and the liquid droplets 2.

(23) The transportation of droplets according to the present invention may occur at room temperature. Room temperature desolvation will occur for some solvents that have particularly low boiling points.

(24) The transportation of droplets 2 may occur substantially at atmospheric pressure or at low pressure in a vacuum chamber.