WO2008017884A2

WO2008017884A2 - Vapour generator

Info

Publication number: WO2008017884A2
Application number: PCT/GB2007/050474
Authority: WO
Inventors: Russell Parris
Original assignee: Owlstone Ltd
Priority date: 2006-08-08
Filing date: 2007-08-07
Publication date: 2008-02-14
Also published as: WO2008017884A3; GB0615682D0

Abstract

A vapour generator is described, including a gas inlet, a sample permeation chamber, a sample flow outlet, and a split flow outlet. A gas flow path is defined from the inlet through the permeation chamber to the outlets. A valve or similar for splitting the gas flow is located after the sample permeation chamber. This arrangement ensures that the flow rate of gas passing the permeation source is constant, as is the concentration of analyte carried by the gas. Variation of the split flow to sample flow rate may be used to vary the concentration of analyte entering a measurement device coupled to the vapour generator, such as an ion mobility spectrometer. Also described is a method of manufacturing a permeation source for use in the vapour generator.

Description

Vapour Generator

FIELD OF THE INVENTION

The present invention relates to devices for use in ion mobility spectroscopy, In particular, aspects of the invention relate to a vapour generator. Certain aspects of the invention relate to a permeation source for use in a vapour generator, and to methods of making such, a permeation source.

BACKGROUND TO THE INVENTION

Ion mobility spectrometry is a versatile technique used to detect presence of molecular species in a gas sample. The technique has particular application in detection of explosives, drugs, and chemical agents in a sample, although it is not limited to these applications. Portable detectors are commonly used for security screening, and in the defence industry.

Ion mobility spectrometry relies on the differential movement of different ion species through an electric field to a detector; by appropriate selection of the parameters of the electric field, ions having differing properties will reach the detector at differing times, if at all. Time of flight (TOF) ion mobility spectrometry measures the time taken by ions when subject to an electric field to travel along a drift tube to a detector against a drift gas flow. By varying the electric field ions of different characteristics will reach the detector at different times, and the composition of a sample can be analysed. This form of spectrometry relies on the length of the drift tube for its resolution; the longer the drift tube, the more powerful the detector.

A variation on TOF ion mobility spectrometry is described in US 5,789,745, which makes use of a moving electrical potential to move ions against a drift gas flow towards a detector. A plurality of spaced electrodes are alternately pulsed to generate a moving potential well, which carries selected ions along with it. Field asymmetric ion mobility spectrometry (FAIMS) is a derivative of time of flight ion mobility spectrometry (TOFIMS), which potentially offers a smaller form factor; however, existing designs use moving gas flows and high voltages, which are undesirable for microchip implementations. Scaling is further hindered by molecular diffusion, an effect that becomes significant in the micron regime. Background information relating to FAIMs can be found in L.A, Buryakov et al. IntJ. Mass. Spectrom. Ion Process. 128 (1993) 143; and E.V. Krylov et al. IntJ. Mass. Spectrom. Ion Process. 225 (2003) 39-51; hereby incorporated by reference.

A further modification of FAIMS is described in international patent publications WO2006/013396 and WO2006/046077, the contents of which are incorporated herein by reference. The devices described in these publications make use of an electric field to cause ions to move toward the detector. This allows for a solid state construction which does not require a gas pump or similar, so allowing for greater miniaturisation of the device than would otherwise be possible, as well as a more robust construction.

Accurate calibration of ion mobility spectrometers is important to allow for variations in operating conditions. In particular, the spectrometer response to a particular analyte may vary with environmental conditions; calibration with a test analyte of known concentration may be used to ensure that correction may be made for such variations. Further, analysis of a known concentration of analyte may be used to test the operation of a spectrometer, or to maintain specific environmental conditions within the spectrometer under which measurements may be made.

Typically such calibration is carried out with a vapour generator in combination with a permeation source. The permeation source contains a sample of a known analyte, and is arranged to release the analyte at a predetermined rate, so that a known concentration of analyte may be analysed by the spectrometer. The vapour generator provides gas at a particular flow rate to carry analyte from the permeation source to the spectrometer. Physical characteristics of the gas used in the vapour generator, such as temperature, pressure, and flow rate, may be varied to control the working environment of the spectrometer. Variation of the flow rate will alter the concentration of analyte carried by the flow. However, this can make it difficult to calculate the concentration of analyte entering the spectrometer, leading to deficiencies in calibration. It would be beneficial to have an alternative form of vapour generator.

US 2004/0216508 describes a permeation calibrator. US 5,142,143 describes a preconcentrator for analysing trace constituents in gases by means of a mass spectrometer. GB 2 389 181 describes a sample introduction system for use with analytical instruments such as mass spectrometers. US 4,847,493 describes apparatus for calibrating a mass spectrometer.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention, there is provided a vapour generator comprising a gas inlet, a sample permeation chamber, a sample flow outlet, and a split flow outlet; with a gas flow path being defined from the inlet through the permeation chamber to the outlets; the generator further comprising means for splitting a gas flow between the sample flow outlet and the split flow outlet, such that the gas flow passes the permeation chamber before being split.

Thus the present invention allows a gas flow to pass a permeation source contained within the permeation chamber so as to carry an analyte to a spectrometer, preferably an ion mobility spectrometer. The user may alter gas flow from the sample flow outlet by opening the split flow outlet. This will alter the sample flow rate and hence the concentration of analyte entering the spectrometer. Note, however, that the gas flow is split after the permeation chamber, such that the flow rate of gas passing the permeation source is constant, as is the concentration of analyte carried by the gas at this point. The concentration of analyte entering the spectrometer can be calculated based on the ratio of the split flow rate to the sample flow rate.

The generator may further comprise one or more meters for measuring either or both of the split flow rate and the sample flow rate. The means for splitting the gas flow may comprise any convenient structure; in preferred embodiments of the invention this comprises a three-way valve such as a T split valve or the like. Preferably the means for splitting the gas flow allows the ratio of sample flow to split flow to be varied; alternatively, or in addition, the vapour generator may comprise a valve associated with either or both of the sample flow outlet and/or the split flow outlet, such that the flow through these outlets may be varied. The valves may be needle valves or similar. One or more of the valve(s) may be lockable such that the valve setting may be fixed during manufacture of the device; alternatively, the valve setting may be fixed by the user of the device.

The vapour generator may also or instead comprise means for selectively closing either or both of the sample and split flow outlets. Preferably at least the split flow outlet may be selectively closed, to allow the split flow to be cut off completely.

hi preferred embodiments of the invention, in use the split flow may preferably be maintained at a constant rate. The constant rate may be predetermined by the user; that is, the constant rate is set before use by the user, but while in use the split flow rate is maintained at a constant level. Alternatively the rate may not be user-settable.

One advantage of maintaining a constant split flow rate is that the ratio of split flow to sample flow may be readily calculated simply by determining the sample flow rate.

The sample flow, in use, may be variable. In typical embodiments of the present invention, the sample flow rate may be from 40 to 500 ml / min, while the split flow rate may be from 40 to 500 ml / min.

In certain embodiments of the invention, the vapour generator may further comprise means for introducing gas into the sample flow which has not passed through the permeation chamber. This additional flow, termed the makeup flow, is generally larger than the sample flow. For example, a branch of the gas flow path may lead directly from the gas inlet to the sample flow outlet, with appropriate valves, pressure regulators, and the like. The means may be arranged so as to maintain the total of the sample flow rate and the makeup flow at a substantially constant level regardless of the split flow rate, and/or regardless of the sample flow rate. This has the benefit of maintaining a constant flow rate into the spectrometer, while the analyte concentration may vary depending on the split flow rate.

The vapour generator may comprise a permeation source in the permeation chamber. Preferably the permeation source is removable, and is also preferably replaceable. The vapour generator may comprise a temperature controller for regulating the temperature of the permeation chamber; this may comprise a heater, hi some circumstances it may be desirable to maintain the permeation chamber at above ambient temperature. Typically the temperature may be varied from ambient temperature to around 120⁰C. The vapour generator may comprise a gas source connected to the gas inlet. The gas source may be air, or may comprise one or more inert gases; for example, nitrogen. The generator may comprise means for regulating pressure of gas in the gas inlet; typically a gas pressure of around 50 psi will be used.

The vapour generator may comprise a dehumidifier, for removing or regulating moisture in the gas flow.

Preferably the sample flow outlet is connected to a spectrometer inlet.

The generator may further comprise a sampling means, for example, a sampling trap or the like, connected to the split flow outlet. This may be used to monitor the analyte levels within the split flow.

The generator may also comprise one or more displays for displaying parameter information. In particular, the flow rates of either or both of the split flow and sample flow, and the temperature of the permeation chamber, may be displayed.

According to a further aspect of the present invention, there is provided a method of operating a vapour generator, the method comprising the steps of: passing a gas flow through a permeation chamber containing a permeation source; splitting the gas flow into sample and split flows; and passing the sample flow into a spectrometer. The split flow may be maintained at a substantially constant rate. Alternatively, the split flow may be varied. The method may further comprise the step of introducing additional gas into the sample flow to maintain the sample flow at a substantially constant rate.

The method may also comprise the step of heating the permeation chamber.

The method may comprise initially setting the split flow rate to substantially zero, and subsequently increasing the split flow rate.

The method may comprise the step of comparing the split flow rate with the sample flow rate to calculate the sample concentration within the sample flow. Alternatively, or in addition, the method may comprise measuring the sample concentration within the split flow, and calculating the concentration within the sample flow based on this measurement.

The vapour generator described herein may use a permeation source as a source of a known concentration of analyte. Conventional permeation sources typically comprise a known mass of analyte within a glass vial; the vial is plugged with a porous stopper to permit the analyte to diffuse from the vial. However, such vials are fragile and costly to produce. We describe herein an alternative production method.

According to an aspect of the present invention there is provided a method of manufacturing a permeation source comprising providing a tube closed at a first end; introducing an analyte into the tube; inserting a permeable polymer plug into the open second end of the tube; introducing a liquid polymer precursor and curing agent into the tube adjacent the plug; and allowing the liquid polymer to cure to form a plug.

Either or both of the polymers are preferably a plastics material, and more preferably an elastomer material. The two polymers may be the same or different.

The permeable polymer permits analyte to diffuse from the tube at a known rate. Varying the thickness of the liquid polymer, and hence the subsequently formed plug, will vary the diffusion rate of the analyte. Use of a preformed polymer plug alone will typically not provide a suitable seal to the tube, while use of a liquid polymer alone will not sit in the desired location within the tube while it cures. Thus the use of a first plug provides an initial seal on which the liquid polymer may be located. The liquid will form an improved seal with the original plug.

The method may also comprise the step of crimping the second end of the tube to improve the seal.

The preformed polymer plug is preferably relatively thin when compared to the depth of liquid polymer added.

In preferred embodiments of the invention the preformed polymer plug and the liquid polymer comprise the same polymer; in particularly preferred embodiments the polymer is PDMS (polydimethylsiloxane). Other appropriate polymers or elastomers may be used, for example, polystyrene. Alternatively, the two polymers may be different; selection of appropriate materials will depend on the desired permeation rate, curing times, manufacturing requirements, and the like. The liquid polymer may also comprise a thinning agent; for example a solvent; for example toluene. This improves the seal between the polymer and the tube. The liquid polymer may comprise an analyte material incorporated therein.

The tube preferably comprises a permeable polymer, although the permeability of the tube to the analyte is preferably lower than the permeability of the elastomer. In preferred embodiments the polymer is PTFE. Other suitable materials may be used.

The tube may be closed at the first end by a polymer plug; this may be of the same material as the polymer plug and / or the liquid polymer used in the second end of the tube. Alternatively the first end of the tube is closed by a polymer plug; preferably a plastic plug; more preferably a PTFE plug. The tube may be crimped at the first end.

The method may further comprise introducing a magnetic material (that is, a material which is attracted to a magnet) adjacent one end of the tube; preferably the first end. Preferably the magnetic material is located outside the closure of the end of the tube. In certain embodiments, the magnetic material may comprise a nickel plug, bead, or the like. Alternatively, iron or steel may be used. This allows the permeation samples to be lifted and transported using magnetism, and allows them to be easily introduced to and replaced from a permeation chamber.

In a variation of this method, the closure at the first end of the tube may be formed using a polymer plug / liquid polymer combination, hi this embodiment, the closure at the second end of the tube may be formed in the same way, or may be formed simply by insertion of a preformed plug. Thus the present invention also provides a method of manufacturing a permeation source comprising providing a tube; inserting a permeable polymer plug into an open first end of the tube; introducing a liquid polymer and curing agent into the tube adjacent the plug; allowing the liquid polymer to cure to form a plug, so closing the first end of the tube; and introducing an analyte into the tube. The method may also comprise the step of forming a closure in an open second end of the tube. The remaining optional features of the method of the invention described above will apply equally to this method.

The present invention also provides a permeation source comprising a tube containing an analyte, the tube being closed at first and second ends, with the closure at the second end comprising first and second portions together forming a permeable polymer plug. The first and second portions may comprise the same polymer material.

The tube may be closed at the first end by a polymer, preferably plastic, preferably

PTFE plug. The tube may further comprise a magnetic material location adjacent one end thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects of the present invention will now be described by way of example with reference to the accompanying drawings, in which

Figure 1 shows a flowchart of the gas flow within a vapour generator in accordance with an embodiment of the present invention;

Figure 2 shows the expected concentration of analyte (benzene) with different split and sample flows using the vapour generator of Figure 1; Figure 3 shows the manufacturing process for producing a permeation source in accordance with an embodiment of the present invention; and

Figure 4 shows sample permeation rates from a range of permeation sources produced in accordance with the process of Figure 3.

DETAILED DESCRIPTION OF THE DRAWINGS

Referring first of all to Figure 1, this shows a flowchart of the gas flow path within a vapour generator according to an embodiment of the present invention. The generator 10 comprises a gas inlet 12, which leads to a pressure regulator 14 and into a permeation chamber 16. The flow leads from the permeation chamber to a T split valve 18, which splits the gas flow into sample flow 20 leading to a sample outlet 22, and a split flow 24 leading to an on/off valve 26 and split outlet 28.

In use, a gas supply, such as of compressed air, is connected to the gas inlet 12, and the sample outlet 22 is connected to the inlet of an ion mobility spectrometer. A permeation source containing an analyte of known permeation rate is located within the permeation chamber 16. The chamber 16 is heated, and gas flows from the inlet via the pressure regulator (which maintains gas flow at 15 psi) to the permeation chamber. Here the gas flow picks up analyte at a known concentration.

As the gas flow plus analyte reaches the T valve 18, it splits into the sample flow and the split flow. Initially the split flow on/off valve 26 is closed, such that the split flow rate is zero, and the entire gas flow constitutes the sample flow. This passes through the sample outlet 22 into the spectrometer, where the known concentration of analyte may be used to calibrate the spectrometer.

The split flow on/off valve 26 is then opened, with the split flow being set at a constant rate; for example, 50 ml / min. This portion of the total flow is vented from the vapour generator. The sample flow 20 is therefore reduced by a corresponding amount, and the concentration of analyte entering the spectrometer reduced accordingly. The ratio of the split and sample flows may be used to calculate the mass and concentration of analyte entering the spectrometer, as the total concentration in the total flow is known.

Figure 2 shows a hypothetical example of analyte (benzene) concentration in sample flow for various values of split flow rate and sample flow rate.

In certain embodiments of the invention, additional gas may be reintroduced into the sample flow to maintain this flow at a constant rate as the split flow increases, hi this way the concentration of analyte will decrease but the flow rate will not. This may have advantages for use in circumstances where the flow rate and gas pressure are desired to be kept relatively constant.

As mentioned above, the permeation chamber of the vapour generator contains a permeation source. Figure 3 shows a method of manufacturing such a source. At one end of a length of V" PTFE tubing 40 a PDMS plug 44 of known thickness and diameter is inserted at the required depth. The remaining space is filled with a silicon elastomer and curing agent mix 46 to the top of the tube. The mix 46 may be thinned using a suitable solvent if desired. The permeation source is then baked at 100⁰C until the elastomer / curing agent mix has set. The permeation source is then filled with the chemical compound of choice and a piece of PTFE plug 42 is used to block the other end or the process is repeated with the elastomer and curing agent to form another PDMS plug. Finally a magnetic plug 48 (that is, a plug which is attracted to a magnet; the plug itself is not necessarily magnetised) is inserted at one end of the tubing.

Once equilibrated the chemical compound will permeate out from the permeation source at a steady rate as long as the temperature is constant. The permeation rate can be affected by increasing the length of the PDMS plug or by using a PDMS plug at both ends. Figure 4 shows the effect of different PDMS plug lengths on permeation rate from the tube.

Claims

1. A vapour generator comprising a gas inlet, a sample permeation chamber, a sample flow outlet, and a split flow outlet; with a gas flow path being defined from the inlet through the permeation chamber to the outlets; the generator further comprising means for splitting a gas flow between the sample flow outlet and the split flow outlet, such that the gas flow passes the permeation chamber before being split.

2. The vapour generator of claim 1, further comprising one or more meters for measuring gas flow through either or both of the split flow outlet and sample flow outlet.

3. The vapour generator of claim 1 or 2, wherein the means for splitting the gas flow comprises a three-way valve.

4. The vapour generator of claim 1, 2 or 3, wherein the means for splitting the gas flow allows the ratio of sample flow to split flow to be varied.

5. The vapour generator of any preceding claim comprising a valve associated with either or both of the sample flow outlet and/or the split flow outlet, such that the flow through these outlets may be varied.

6. The vapour generator of any preceding claim comprising means for selectively closing either or both of the sample and split flow outlets.

7. The vapour generator of any preceding claim wherein in use the split flow may be maintained at a constant rate.

8. The vapour generator of claim 7 wherein the constant rate may be selectively adjustable by the user.

9. The vapour generator of any preceding claim wherein the sample flow rate, in use, is variable.

10. The vapour generator of any preceding claim further comprising means for introducing gas into the sample flow which has not passed through the permeation chamber.

11. The vapour generator of claim 10 wherein the gas introducing means is arranged so as to maintain the total flow rate comprising the sample flow and the introduced gas at a substantially constant level regardless of the split flow rate.

12. The vapour generator of claim 10 or 11 wherein the gas introducing means is arranged so as to maintain the total flow rate comprising the sample flow and the introduced gas at a substantially constant level regardless of the sample flow rate.

13. The vapour generator of any preceding claim comprising a permeation source in the permeation chamber.

14. The vapour generator of any preceding claim comprising a temperature controller for regulating the temperature of the permeation chamber.

15. The vapour generator of any preceding claim comprising means for regulating pressure of gas in the gas inlet.

16. The vapour generator of any preceding claim further comprising a sampling trap or the like connected to the split flow outlet.

17. The vapour generator of any preceding claim comprising one or more displays for displaying parameter information.

18. A method of operating a vapour generator, the method comprising the steps of: passing a gas flow through a permeation chamber containing a permeation source; splitting the gas flow into sample and split flows; and passing the sample flow into a spectrometer.

19. The method of claim 18 wherein the split flow is maintained at a substantially constant rate.

20. The method of claim 18 further comprising the step of introducing additional gas into the sample flow to maintain the sample flow at a substantially constant rate.

21. The method of claim 18 comprising the step of heating the permeation chamber,

22. The method of claim 18 comprising initially setting the split flow rate to substantially zero, and subsequently increasing the split flow rate.

23. The method of claim 16 comprising the step of comparing the split flow rate with the sample flow rate to calculate the sample concentration within the sample flow.

24. A method of manufacturing a permeation source comprising providing a tube closed at a first end; introducing an analyte into the tube; inserting a permeable polymer plug into the open second end of the tube; introducing a liquid polymer precursor and curing agent into the tube adjacent the plug; and allowing the liquid polymer to cure to form a plug.

25. The method of claim 24 comprising the step of crimping the second end of the tube to improve the seal.

26. The method of claim 24 wherein the preformed polymer plug is relatively thin when compared to the depth of liquid polymer added.

27. The method of claim 24 wherein the preformed polymer plug and the liquid polymer comprise the same polymer.

28. The method of claim 27 wherein the polymer is PDMS.

29. The method of claim 24 wherein the tube comprises a permeable polymer.

30. The method of claim 29 wherein the tube comprises PTFE.

31. The method of claim 24 wherein the tube is closed at the first end by a polymer plug.

32. The method of claim 24 further comprising introducing a magnetic material adjacent one end of the tube.

33. A method of manufacturing a permeation source comprising providing a tube; inserting a permeable polymer plug into an open first end of the tube; introducing a liquid polymer precursor and curing agent into the tube adjacent the plug; allowing the liquid polymer to cure to form a plug, so closing the first end of the tube; and introducing an analyte into the tube.

34. A permeation source comprising a tube containing an analyte, the tube being closed at first and second ends, with the closure at the second end comprising first and second portions together forming a permeable polymer plug.