GB2392114A

GB2392114A - Temperature controlled membrane interface device.

Info

Publication number: GB2392114A
Application number: GB0319822A
Authority: GB
Inventors: Colin Stephen Creaser; David Gomez Lamarca; Anthony Peter New
Original assignee: Glaxo Group Ltd
Current assignee: Glaxo Group Ltd
Priority date: 2002-08-23
Filing date: 2003-08-22
Publication date: 2004-02-25
Anticipated expiration: 2023-08-22
Also published as: GB2392114B; GB0319822D0

Abstract

A temperature controlled membrane interface (MI) device comprises a housing with an integral heater, the interior of the housing being divided into first and second chambers by a semipermeable membrane with the housing having a sample inlet and outlet located in the first chamber and a gas inlet and gas outlet in the second chamber. The heater may be an insulated nichrome alloy heating wire provided around, within ir inside the housing. The semipermeable membrane may be a tube, a sheet or a thin film and may be made of silicone. The device may be in the form of a cartridge. In use, the device can be used as an inlet device for a variety of analytical instrumentation such as that used in mass spectrometry or gas chromatography.

Description

23921 14

TEMPERATURE CONTROLLED MEMBRANE INTERFACE DEVICE

The present invention relates to devices for use in the analysis of analyses in liquid or gas samples. Specifically, the invention relates to a temperature controlled membrane 5 interface which can be used as an inlet device with a variety of analytical instrumentation, including mass spectrometry and gas chromatography.

Membrane inlet (or introduction) (Ml) has been shown to be a rapid and sensitive

technique for the determination of volatile organic compounds (\/OCs) in aqueous 10 streams, air samples, and process monitoring applications. The principles and recent developments in membrane inlet mass spectrometry (MIMS) have been discussed In a number of reviews and have been shown by Ketola et al. (Talanta (1997) 44, 373) and Harland et al. (Sci. Total Environ. (1993) 35, 37) to be superior in many respects to other techniques, including purge and trap-GC/MS, for the determination of VOCs. The 15 sensitivity of MIMS for VOCs is generally high, and detection limits In the parts per billion (ppb) range are possible for many compounds, with non-polar, low molecular weight analyses showing the lowest detection limits. MIMS has been combined with tandem mass spectrometry (MS/MS) and on-line cryotrapping and rapid GO separation to improve selectivity and reduce detection limits to the low-ppt (parts per trillion) range for selected 20 VOCs (Launtsen et al Rapid Commun. Mass Spectrom. (1990) 4, 401 and Creaser et al Anal. Commun. (1999) 36, 383).

The observation that Ml interfaces perform better for non-polar, low molecular weight VOCs than for more polar, less volatile, compounds, particularly with the use of silicone 25 membranes, demonstrates the limit of applicability of the simple Ml technique. A number

of papers have been published on techniques to expand the range of compounds compatible with Ml. Lauritsen et al. (Rapid Commun. Mass Spectrom. (19g5) 9, 591) described an in-source membrane inlet system for the detection of semi-volatile organic compounds (SVOCs) in aqueous solution, in which the sample was passed through a 30 hollow-fibre membrane positioned in a modified El mass spectrometer source. Interruption of the sample flow led to rapid heating of the membrane by the El filament situated close to the membrane surface. This approach reduced limits of detection for a range of phenols, phenanthrene, and phenoxyacetic acid, showing gains in sensitivity up to 250 times compared to conventional MIMS. A second-generation system employing the same 35 principles was also devised (Lauritsen & Ketola Anal. Chem. (1997) 69, 4917), but instead

of the sample flow being interrupted, an air plug was passed through the membrane while heating took place. This resulted in a more rapid heating rate, giving a narrower Resorption profile, and the determination of caffeine in tea and coffee samples was demonstrated with good precision. In the configuration adopted by Maw et al. (J.

5 Chromatog., A (1996) 750, 141) in the analysis of fermentation suspensions, analyses were pre-concentrated on a pneumatically driven membrane probe before desorption at 1 SAC.

The use of laser desorption in the determination of SVOCs by MIMS was reported by Soni 10 et al. (Anal. Chem (1998) 70, 3103 and Rapid Commun, Mass Spectrom. (1998) 12, 1635). A low-power carbon dioxide laser was used to irradiate the vacuum side of a sheet membrane held in a directinsertion (in-source) membrane probe, resulting in desorption of the permeate molecules with little fragmentation. The probe was mounted either in a machined housing connected to a transfer line or directly into the spectrometer ion source 15 region. The technique was demonstrated for the determination of a group of polyaromatic hydrocarbons (PAHs) at the low-ppb level. A development of laser desorption MIMS used resonance-enhanced multiphoton ionisation for the determination of PAHs in water at a much lower (ppt) levels than previously possible. The increase in sensitivity was attributed to the selectivity of the multiphoton ionisaton (MPI) process for the PAHs over the 20 membrane material and residual background compounds present in the spectrometer

vacuum chamber.

All the above methods are effective in the determination of SVOCs in water but in most cases require elaborate and often lengthy modifications to either the membrane interface 25 or the spectrometer ion source, or both.

The Ml technique has been applied successfully to sem'-volatile organic compounds (SVOCs) using in-membrane pre-concentration techniques (Creaser et al Anal. Chem. (2000) 72(13), 2730). In-membrane pre-concentration consists of the retention of the 30 analyses in the membrane while the sample is being pumped through the system (injection bme). The membrane is then dried (drying step) by pumping air or an inert gas across the surface of the membrane, to eliminate water from the system, thus avoiding signal suppression, and therefore enhancing the sensitivity. When the membrane is dry it is heated, allowing analyses to be released from the membrane and into a stream of helium 35 which is directed into a detector e.g. mass spectrometer source.

The main advantage of Ml in comparison to other techniques is the discrimination against the matrix, allowing selected analyses to cross the membrane preferentially. Therefore extensive sample preparation such as extraction Is not required, and it makes this 5 technique very useful for monitoring volatile and semi-volatile materials from complex matrices for applications such as environmental analysis and the monitoring of biological and chemical processes (Creaser et al Analytical Chemistry (2002), 74(1), 300; Creaser et al Analytica Chimica Acta (2002) 454, 137; Kotiaho et al Process Control and Quality (1998)1 1 (1), 71).

One disadvantage of Ml is the analysis of very complex samples. As there is no chromatographic separation, most compounds are desorbed without being separated, making identification complicated.

15 The main disadvantage of IMP-MI is the fact that existing technology uses a GC oven or the Ion source of a mass spectrometer to heat the membrane to the desired temperature.

If a GC oven is used, the time required to heat (and cool) the mass of the oven significantly increases the analysis time. The release of materials from the membrane heated in this way is slow, limiting the chromatography obtainable if the membrane inlet 20 was linked to a GC for example.

The present invention overcomes the above problems.

Accordingly, in first aspect the present invention provides a membrane interface 25 comprising a housing defining an interior space which is compartmentalized by a semi-

permeable membrane into a first chamber and a second chamber; the housing having a sample inlet and a sample outlet positioned in the hrst chamber, and a gas Inlet and a gas outlet positioned in the second chamber; characterized in that the housing is heated directly by integral heating means.

The housing may be made of any inert, conductive material capable of withstanding extremes of temperature. Preferably the housing may be constructed from stainless steel, for example from stainless steel tubing.

The semi-permeable membrane is suitably a hollow fibre (tubular), sheet or thin film composite membrane. Preferably the membrane is a hollow fibre (tubular) membrane. The membrane should be made of a suitable material. Examples of suitable hydrophobic membranes include polydmethylsiloxane (silicone) and polypropylene. Examples of 5 suitable hydrophilic membranes include Nafion0. Preferably the membrane is made of silicone. Most preferably the membrane is a hollow fibre silicone membrane.

The integral means for heating the housing may be any means capable of quickly heating the housing directly in a controlled and controllable manner. For example, the heating 10 means should be capable of heating the housing at fast rates of up to 10 C so. Preferably the heating means comprises a heating wire provided directly around within or inside the housing, and connected to an automatic or manual control. In a particularly preferred embodiment the housing is constructed of metal tubing (such as stainless steel tubing) and the heating wire is provided directly around, within or inside the housing as a coaxial 15 helical coil. "Integral" in this context means that the heating means is part of the housing structure rather than providing a remote source of heat. "Directly" in this context means that the housing is heated by being in contact with or in very close proximity to a dedicated heat source, as distinguished from "indirectly" heated e.g. by being placed in an oven.

(However, the devices of the Invention may be used in a GC oven if it is desired to 20 regulate the external temperature.) A particularly suitable method of heating is an insulated nichrome alloy heater wire, which may be encased by a stainless steel outer sheath.

25 As mentioned above the membrane must be positioned within the housing so as to create at least two chambers in the interior space of the housing. Thus, a tubular membrane within the housing will create two chambers: one within the walls of the tubular membrane and one on the outside of the membrane.

30 The sample inlet and sample outlet in the housing should be positioned to enable a liquid or gaseous sample to flow into and out of the first chamber created by the housing and the membrane. The gas inlet and gas outlet in the housing should be positioned to enable a gas stream to flow into and out of the second chamber created by the housing and the membrane. In practice the sample inlet and outlet may be one and the same, and/or the 35 gas inlet and outlet may be one and the same.

In a preferred embodiment, the membrane is a tubular membrane, the first chamber is on the outside of the tubular membrane, and the second chamber is within the tubular membrane. In a preferred embodiment the housing may be provided as a layered construction i.e. at least an Inner housing layer and an outer housing layer. In this embodiment the membrane will suitably be supported within the inner layer of the housing, while means for heating the housing will suitably be supported by the outer layer of the housing. The inner 10 layer of the housing will be adapted to fit Into the outer layer of the housing in a close fit, so that both the inner and outer layers of the housing may be heated by the integral heating means.

VOCs when analysed by Ml may not be retained significantly in the membrane, giving 15 continuous infusion results, unless Ml is linked to another technique such as cryotrapping.

(Previous reported examples in the literature use a cryotrap to store desorbed analyses from the membrane before they are released.) In order to quantify VOCs by Ml, equilibration of the signal (obtained when diffusion of the analyte through the membrane reaches steady state) is needed, and sometimes it can be a long process. The main 20 advantages of introducing VOCs to a system using Ml is the increase in limit of detection (I.o.d.) and the fact that little or no equilibration time is required for quantitation.

In some cases it is useful to be able to pre-concentrate volatile compounds in the membrane. To do this it is necessary to cool the membrane to sub-ambient temperatures.

25 Accordingly, optionally there is a small cavity between the inner and outer layers of the housing, In which may be provided means for cooling the housing. For example, the outer layer of the housing may be provided with an inlet into the cavity, through which may be supplied into the cavity a stream of cooling gas (such as nitrogen or helium). The gas can be suitably cooled by being passed through a supply pipe, which is placed inside a Dewer 30 flask, containing a suitable coolant such as liquid nitrogen (-195 C). In this way the housing can be cooled when required, enabling experiments using the membrane inlet in which the membrane may be cooled to suambient temperatures. For the analysis of volatile compounds in air samples, the membrane needs to be cooled to temperatures below 0 C.

Optionally, the housing may be insulated. For example, the housing may be surrounded by an external insulating layer Any suitable insulating material may be used.

Additionally or alternatively, optionally the inner part of the housing (containing the 5 membrane) will be removable from the outer part of the housing (having the heater). This has the advantage of allowing the membrane to be easily and quickly replaced as a "cartridge". Accordingly, in second aspect the present invention provides a replaceable membrane 10 cartridge, comprising an inner housing layer defining an interior space which is compartmentalized by a semi-permeable membrane into a first chamber and a second chamber; the inner housing layer having a sample inlet and a sample outlet positioned in the first chamber, and a gas inlet and a gas outlet positioned in the second chamber, wherein the inner housing layer is adapted to fit within an outer housing layer which is 15 provided with Integral means for heating the inner and outer housing layers.

For example, in this aspect (as in the previous aspect) the inner and outer housing layers may take the form of concentric tubes, the outer tube having a heating wire coiled around either the inside or the outside.

In third aspect the present invention provides the use of a membrane interface device according to the first aspect of the invention in an analytical process for detection of volatile and/or semi-volatile organic compounds in a liquid or gas sample.

25 In fourth aspect the present invention provides the use of a replaceable membrane cartridge according to the second aspect of the invention in an analytical process for detection of volatile and/or sem'volatile organic compounds in a liquid or gas sample.

In the third and fourth aspects of the invention, suitable analytical processes would involve 30 the use of mass spectrometry, gas chromatography or a combination of gas chromatography and mass spectrometry.

Use of the TCMI devices of the present Invention typically may comprise the steps of:

1) pumping the sample through the membrane interface via the sample inlet and sample outlet, achieving retention of analyses in the membrane (injection step); 2) drying the membrane with the use of an inert drying gas (drying step); 3) heating the membrane using the integral heating means.

The use of the membrane interface may also involve the step of cooling of the membrane either by turning the heating means down (or oh, or supplying cooling means. This allows volatile analyses to be pre- concentrated in the membrane, as described above.

10 In the third and fourth aspects of the invention the membrane may be heated in a stepwise fashion to allow successive release of analyses depending on volatility.

Alternatively, the use of the TCMI devices of the present invention may comprise the step of pumping the sample through the membrane interface via the sample inlet and sample 15 outlet, thereby achieving substantially continuous permeation of the analyses through the membrane i.e. the analyses pass through the membrane without being retained in a retention stage.

To effect these aspects of the invention conduits to supply and remove liquid or gaseous 20 sample may be connected to the sample inlet and outlet of the membrane interface according to the first aspect or the membrane cartridge according to the second aspect.

Suitable conduits are well known in the art. A pump such as a peristaltic pump may be used to direct sample flow through the device of the invention during the injection step.

25 The drying step may be needed because the presence of air and water in the interface results in membrane oxidation, therefore shortening the membrane life. The presence of water also creates ion suppression In the El source The drying step may be achieved by pumping air or an inert gas across the surface of the membrane, to eliminate water from the system, thus avoiding signal suppression, and therefore enhancing sensitivity.

The heating step allows analyses to be released from the membrane, which may then be directed out of the membrane inlet and into a suitable detector (e.g. mass spectrometer source). This may be achieved via a stream of gas such as helium which can be directed through the membrane interface via the gas inlet and gas outlet. To effect these aspects 35 of the invention the gas outlet of the membrane interface according to the first aspect or

the membrane cartridge according to the second aspect may be connected to a MS or GC device using a suitable conduit such as methyl deactivated, uncoated fused silica capillary column. A similar conduit may be used to connect the gas inlet to a suitable gas source, such as a helium source. (In use, the injector of a GC may be used for this purpose.) In 5 this way a flow of gas such as helium may be directed through a device of the invention for transfer of analyses into the MS, GC or other detector.

In the devices of the first two aspects of the invention, for effective use, the device should be made vacuum and water fight when in use, for example by the use of stainless steel 10 compression fittings or other means well known in the art. The membrane may be held in place using any suitable fittings.

Before first use of the device of either the first or second aspect of the invention, it is desirable to condition the membrane. Membrane conditioning techniques well known in 15 the art for MIMS may be applied to the present invention.

The presently claimed invention uses the advantages of membrane inlet mass spectrometry (MIMS), but through use of a directly heated housing allows precise control of the temperature of the membrane. Typically the temperature of the membrane may be 20 controlled between -50 C to 250 C, and the temperature of the membrane can typically be increased by 1 0 C so, compared to typically 1 C so with conventional MIMS techniques using a GC oven. This enables VOCs and SVOCs to be trapped on the membrane then desorbed rapidly either to be focussed (for example on a GC column) or directly analysed (for example using a mass spectrometer).

The rapid heating gives faster analysis time and material is desorbed as a sharper band which allows improved detection or GC chromatography. The present invention extends the range of analyses compared to MIMS through the exacting control of the temperature of the membrane. This allows VOCs and SVOCs to be analysed in the same run which 30 eliminates the need for a separate cryotrap and is an improvement on other GC sampling techniques for example purge and trap.

The devices of the present invention offer significant time saving per analysis. For instance, non pre-treated samples can be analysed with little or no sample preparation

and thus complex sample extraction procedures can be avoided. As a sampling device it can be coupled with GC, GC/MS or directly into the mass spectrometer or other detector.

The use of the present invention is an extension of the application of Ml to encompass the 5 measurement of both VOCs and SVOCs in samples, and has a range of applications in the pharmaceutical industry from the measurement of residual solvent in tablets/drug substance to automated monitoring of components in water, at waste water treatment plants. Since a GC oven is not required for the thermal Resorption stage, the device is comparatively small and so may potentially find utility with small, portable instruments.

Specific embodiments of the invention will now be described by way of the following Examples with reference to the accompanying drawings.

Example 1

Device construction The device is constructed from concentric stainless steel tubes and is illustrated in Figure 1. The inner tube or cartridge (0.1090" o.d. by 0.091" i.d.) contains a stainless steel 20 sample inlet and a sample outlet tube (0.03125" o.d. by 0.020 i.d.) at opposite ends. The sample inlet can be connected to a liquid or gaseous sample or an inert gas stream (such as helium or nitrogen when a drying stage is required). The membrane is placed inside the cartridge, and is connected to a deactivated fused silica tubing (0.25 mm i.d., SGE, Milton Keynes, UK) in each end. Each piece of fused silica is Inserted 5 mm approximately into 25 the membrane. One length of fused silica is connected to a helium supply (for example the injector of a GC can be used for this purpose). The other length of fused silica is connected to a detector or GC column Two PEEK caps are glued to each end of the cartridge, to seal it, to prevent analyte loss.

30 The cartridge is coiled around with electric wire, which was linked to a power supply (Tti 3510 Standard, 0 - 35 V, 0 - 10 A, bench; Farnell, Leeds, UK). A voltage was applied and the temperature was monitored with a thermocouple In contact with the cartridge.

The cartridge is placed inside a T-shaped tube (0.375" o.d. and 0.319" i. d.). The T-shaped 35 tube is connected to a pipe, so that cool gas (helium or nitrogen) can be introduced to cool

the cartridge. The cooling gas pipe is immersed in a dower containing liquid nitrogen or other coolant when sub-ambient temperatures are required as described above. Cooling gas exits the device through both ends.

5 Analvsis of aqueous sample For analysis of an aqueous sample, the TCMI device was linked to a Hewlett Packard HP6890/HP5973 GC/MS configuration (Agilent Technologies, Palo Alto, California, USA).

The interface containing a silicone hollow-fibre membrane (0.635 mm o.d. x 0.305 mm i.d., 10 Dow Coming Silastic, Sanitech, USA) was constructed and located inside the GC oven in place of the capillary GC column. The oven temperature was kept at 40 C and the membrane was heated directly using a heater located inside the device. Samples were pumped through the interface using a peristaltic pump (Watson-Marrow Bredel Pumps Limited, United Kingdom). When no sample was being introduced into the interface, the 15 outer walls of the membrane were flushed with Inert gas (flow of 50 ml min '), in order to dry the membrane.

The temperature of the membrane was measured with a thermocouple, and the parameters that were modified were intensity and voltage.

Experimental work demonstrating the performance of the TCMI device and comparing the response given by MIMS and by TCMI-MS was carried out with DMSO. Figure 2 shows two overlapped ion chromatograms of mass m/z 63 (characteristic ion for DMSO) (a) using MIMS (broad peak) and (b) using the device of Example 1. The peak width at half 25 height obtained by TCMI is over 5 times narrower than the peak obtained by MIMS, while the height is almost 10 times greater These results show that TCMI is capable of producing sharper peaks and higher responses. The cycle time is also reduced by using the electrically heated device, which can heat the membrane much quicker than a GC oven, reducing therefore the desorption step.

Both analyses consisted of an injection (3 ml min') of the aqueous sample for 5 minutes and a 14 minute drying step flushing helium (at 50 ml min') through the outer wall of the membrane. During this time the membrane was kept at 40 C For MIMS the membrane was heated using the GC oven up to 200 C at a gradient of 45 C min' and then 35 immediately cooled down at the same rate. When using the TCMI-MS technique, the

membrane was heated to 220 C immediately (a voltage of 3.5 V and an intensity of 2.7 A revere used). The membrane was kept at this temperature for 30 seconds and then the electrical supply was switched off, cooling the device immediately.

5 Example 2

Device construction The device is constructed from three concentric stainless steel tubes. The inner tube or 10 cartridge (Figures 3 and 4) (0.1090" o.d. by 0.091" i.d.) contains a stainless steel sample inlet and a sample outlet tube (0.03125" o.d. by 0.020" i.d) at opposite ends of the cartridge. The sample inlet can be connected to a liquid or gaseous sample or an inert gas stream (such as helium or nitrogen when a drying stage is required). The membrane is placed inside the cartridge, and is connected to a deactivated fused silica tubing (0 25 mm 15 i.d., SGE, Milton Keynes, UK) in each ending. Each piece of fused silica is inserted approximately 5 mm into the membrane One length of fused silica is connected to a helium supply (for example the injector of a GC can be used for this purpose). The other length of fused silica is connected to a detector or GO column. Two PEEK caps are glued to each end of the cartridge, to seal it, to prevent analyte loss.

The cartridge is placed inside a T-shaped tube (0.375" o.d. and 0.319" i. d.). Heating wire is coiled around the inner wall of the T-shaped tube and a thermocouple tK type, RS Components Ltd., UK) was located within the T-shaped tube. The T-shaped tube is connected to a pipe, so that cool gas (helium or nitrogen) can be introduced to cool the 25 cartndge. The cooling gas pipe is immersed in a Dewer flask containing liquid nitrogen or other coolant when sub-ambient temperatures are required. Cooling gas exits the device through both ends.

The heating wire (Thermocoax, Suresnes, France) is a thin nichrome alloy heater wire 30 encased in and isolated from a stainless steel outer sheath by a powdered Insulation. The total heating element used is very low in mass, being only 0.5 mm diameter and around 300 mm long, and is brazed to the T-shaped tube for good thermal transmission. Keeping the whole heater assembly low mass allows heating rates up to 20 C s-' to be achieved, although during the experiments rates used oscillated between 5 and 1 0 C s'. The heater 35 wires were custom terminated (Cambridge Scientific Instruments, Ely, UK) to 1 strand 0.3

mm diameter nickel wire insulated with vidaflex sleeving. The custom termination was via a stainless steel crimp connection potted with a high temperature ceramic fibre adhesive The heating wires and the thermocouple are connected to a control box. This control box was used to regulate the temperature or temperature gradient of the interface to the 5 desired value by controlling the power applied to the heater. The outer stainless steel tube (0.700n o.d., 0.621" i.d.) is used to insulate the cartridge and the carrier gas tube. The T-

shaped tube is introduced inside the outer tube, and the space between is fined with insulating material.

10 The whole assembly is located in a stainless steel holder, which may be attached to the detector or GO wall.

Analysis of aqueous sample 15 The TCMI device of this example was used for the detection of nitrogen containing compounds such as nmethylpyrrolidinone (NMP) and tetramethylethylenediamine (TMEDA), and resulted in sharper peaks and shorter analysis times for the TCMI/MS technique in both cases, compared with conventional IMP-MIMS.

20 Sub-ambient analysis The operation of the TCMI device at sub-ambient temperatures was tested for benzene and toluene using a Varian Saturn 4D (Varian Associates, Walnut Creek, CA, USA) quadrupole ion trap mass spectrometer A schematic of the TCMI device for suambent 25 analysis is shown in Figure 5. Both compounds were analysed in the low ppb region (33 PpbV of benzene and 28 pPbV (vol/vol) of toluene) for evaluation of the technique. See Figures 6 and 7.

An air sample containing toluene or benzene was introduced into the interface for 3 30 minutes, whilst the membrane was held at -20 C with the aid of the cooling gas. The membrane was flushed with nitrogen (50ml mind) for two minutes and the interface was then electrically heated to 100 C and cooled to -20 C again. The heating cycle was repeated twice to clean the membrane before introduction of another sample. Figures 6

and 7 show that both toluene and benzene may be pre-concentrated in the TCMI interface 35 at sub-ambent temperatures and then thermally desorbed into the mass spectrometer.

Example 3

Device construction The TCMI device was similar to the device of Example2, except that the sample inlet and sample outlet were located at the same end of the cartridge (Figure 8). Also, the thermocouple was brazed to the inner wall of the T-shaped tube.

10 The whole assembly (Figure 9) is located in a stainless steel holder, which may be attached to the detector or GC wall.

Analysis of aqueous samples 15 The TCMI device of this example was tested with a mixture of volatile and semi-volatile compounds. 2-chloro-5trifluoromethylanline (CFA) and 3-bromopyridine (3BP) behave like volatile compounds, as they diffuse through the membrane at room temperature. NMP and TMEDA pre-concentrate in the membrane at room temperature and are released when the membrane is heated. Figure 10 shows the single ion responses for m/z 58, 98, 20 158 and 195 (characteristic mass ions for TMEDA, NMP, 3BP and CFA) The concentration of each analyte was 100 ppm. The oven was kept at room temperature (25 C) during the experiment, and the sample was infused for 5 minutes. The membrane was directly heated to 200 C after a drying step of 6 minutes.

25 TCMI-GC/MS

The TCMI device was linked to a GC column located inside a GC oven, which was interfaced to a mass spectrometer for these experiments. The instrument used was a Hewlett Packard HP6890/HP5973 GC/MS (Agilent Technologies, Palo Alto, California, 30 USA), and the GC column was a 25 m x 0.22 mm i.d. with film thickness 0.25,um BP1 column (SGE, Milton Keynes, UK).

The TCMI device was linked on one side to the injector of the gas chromatograph (membrane Inlet) and on the other side to the GC column (membrane outlet). A diagram of 35 the device can be seen in figure 11.

The system was tested for a mixture of nitrogen containing compounds, CFA, 3BP, NMP and TMEDA (100 ppm in pure water).

5 Samples were introduced into the TCMI membrane interface at room temperature for 5 minutes, and then the membrane was flushed with nitrogen (50 ml min-') for 5 minutes. A high percentage of 3BP and CFA permeated the membrane at room temperature, whilst NMP and TMEDA were fully retained in the membrane. Then the membrane was heated directly to 200 C at a rate of 4 C s', so that the analyses that had pre-concentrated in the 10 membrane (NMP and TMEDA mainly, plus some CFA and 3BP) were released onto the GC column. The GC program was as follows: 3 minutes at 35 C, then heat to 200 C at 25 C mine', and hold at 200 C for 10 minutes. The program was started once the membrane had reached 200 C.

15 Although 3BP and CFA diffuse through the membrane continuously during the sample injection and the drying time, both analyses are retained in the GC column, and are released as a peak with the less volatile analyses NMP and TMEDA when the column is heated. Both peaks tail slightly, as do NMP and TMEDA. The single ion responses (m/z 58 for TMEDA, m/z 98 for NMP, m/z 158 for 3BP and m/z 195 for CFA) are shown in 20 Figure 12.

Example 4

Bioreactor monitoring A 5 litre bioreactor containing activated sludge was set up. The pH was fixed to 7.00 and the temperature was set to 35 C, and the containing was stirred to 150 rpm for oxygen to dissolve. The bioreactor was spiked with 25 ppm of CFA, 100 ppm of TMEDA and 100 ppm of 3BP, and a sample of the boreactor medium was extracted and measured online 30 The concentrations obtained using the membrane inlet were 28 ppm for CFA (88% accuracy), 96 ppm for 3BP (96% accuracy) and 91 ppm for TMEDA (91% accuracy).

The TCMI-GC/MS interface was used to identify metabolites obtained during the biodegradation studies on TMEDA, NMP, 3BP and CFA. The metabolites identified by 35 GC/MS were also identified by TCMI-GC/MS. However it is notable that one metabolite

identified by TCMI-GC/MS was not detected by GC/MS. This was 3trifluoromethylaniline, presumably formed by the substitution of the chlorine atom. A possible explanation for detection with TCMI-GC/MS (and not by GC/MS) is that for GC/MS the sample enters the system via an injector held at high temperature especially for the more polar, thermally 5 labile compounds. However, when using the TCMI-GC/MS, the compound is trapped by the membrane, rather than passing through the injector, avoiding high temperatures that could produce thermal decomposition of some compounds.

Example 5

TCMI-GC/MS analysis of VOCs in aqueous samples at suambient temperatures A mixture of benzene, toluene and xylenes in water was anlaysed by TCMIGC/MS to evaluate the potential of the interface for in-membrane preconcentration of VOCs at sub 15 ambient temperatures. These compounds diffuse through the membrane at room temperature and are not preconcentrated in the GO column at 35 C, so a separate cryotrapping step is normally required in Ml-GC/MS methods. The TCMI was therefore cooled to sub-ambient temperatures to pre-concentrate the analyses in the membrane prior to thermal Resorption. The interface was held at -15 C in order to prevent the 20 aqueous sample from freezing in the membrane inlet and interrupting the sample flow.

A satisfactory GO separation was obtained for the desorbed BTEX compounds (see Figure 13) and the analyte responses showed good linearity between 1 and 25 mg l-', with r2 values of 0.9923 (benzene), 0.9941 (toluene), 0. 9996 (m-xylene and p-xylene) and 25 0.9992 (>xylene). The response reproducibility was determined for solutions containing 25 mg 1' of each analyte. The precision (%RSDs, n = 3) was 8.4% (benzene), 4.9% (toluene), 6.2% (m-xylene and p-xylene) and 8.2% (>xylene). Limits of detection (S:N 3:1) in full scan mode were estimated to be 20 fig I ' for benzene, 23,ug 1 ' for toluene, 29 p9 I-' for m-xylene and p-xylene and 21 fig I' for ethylene for a 5 minutes membrane pre 30 concentration time.

Aqueous samples obtained from a former petrol station site were analysed by TCMI GC/MS and the chromatogram obtained for one sample is shown in Figure 13. Peaks A to D (Figure 13) were assigned by retention time and mass spectral data to benzene (m/z 35 78), toluene (m/z 92), (m+p)xylenes (m/z 106) and mxylene (m/z 106) respectively.

Peaks E to I arise from the presence of alkylbenzene with a molecular weight of 120 (CgH'2). Peaks J and K show a molecular ion at m/z 116 and m/z 130 respectively, corresponding to C9H8 and C'oH'o. Peak L shows a molecular ion at m/z 128 (Cathy), assigned to naphthalene, and peaks M and N have molecular ions at m/z 142 (Coo) 5 assigned to 1- methyinaphthalene and 2-methyinaphthalene.

Example 6

TCMI-GC/MS analysis of car exhaust emission samples Car exhaust emission samples were analysed by TCMI-GC/MS at sub-ambient temperatures in order to retain and pre-concentrate volatile organic compounds in the membrane. During the thermal desorption step the analyses were released from the membrane and separated by gas chromatography before entering the mass spectrometer.

A car exhaust sample obtained from a Metro car (1989 registration) was analysed by sub ambient TCMI-GC/MS and the single ion chromatograms are shown in Figure 14a Peaks A to D (Figure 14a) correspond to benzene (m/z 78), toluene (m/z 92), (m+p)-xylenes (m/z 106) and mxylene (m/z 106) respectively on the basis of retention time and mass spectral 20 data. A car exhaust sample collected from a Ford Focus Van (2001 registration) was also analysed by TCMI-GC/MS (Figure 14b). Benzene (m/z 78) and toluene (m/z 92) were detected (peaks E and F) but the xylenes were not detected in this sample. The absence of xylenes in the sample taken from the newer vehicle may be due to the catalytic converter fitted in the newer vehicle. These data show that VOCs in air samples may be 25 pre- concentrated and detected at low levels using TCMI-GC/MS.

Claims

1. A membrane interface comprising a housing defining an interior space which is compartmentalized by a semi-permeable membrane into a first chamber and a second 5 chamber; the housing having a sample inlet and a sample outlet positioned in the first chamber, and a gas inlet and a gas outlet positioned in the second chamber; characterized in that the housing is heated directly by integral heating means.

2. The membrane interface according to claim 1 wherein the heating means 10 comprises a heating wire provided directly around, within or inside the housing.

3. The membrane interface according to claim 2 wherein the heating wire is an insulated nichrome alloy heater wire, optionally encased by a stainless steel outer sheath.

15 4. The membrane interface according to any preceding claim wherein the semi-

penmeable membrane is sudably a tubular, sheet, or thin film composite membrane.

5. The membrane interface according to any preceding claim wherein the semi-

permeable membrane is made of silicone.

6. The membrane interface according to any preceding claim wherein the membrane is a tubular membrane, the first chamber is on the outside of the tubular membrane, and the second chamber is within the tubular membrane.

25 7. The membrane interface according to any preceding claim in which the housing comprises an inner housing layer supporting the membrane and an outer housing layer supporting the means for heating the housing wherein the inner layer of the housing is adapted to fit into the outer layer of the housing in a close fit.

30 8. The membrane interface according to claim 7 wherein there is a cavity between the inner and outer layers of the housing, in which may be provided means for controllably cooling the housing.

9. The membrane interface according to claim 7 or claim 8 wherein the inner housing 35 layer Is removable from the outer housing layer.

10. A replaceable membrane cartridge, comprising an inner housing layer defining an interior space which is compartmentalized by a semi-permeable membrane into a first chamber and a second chamber; the inner housing layer having a sample inlet and a 5 sample outlet positioned in the first chamber, and a gas inlet and a gas outlet positioned in the second chamber, wherein the inner housing layer is adapted to fit within an outer housing layer provided with integral means for heating the inner and outer housing layers.

11. The replaceable membrane cartridge according to claim 10 wherein the inner and 10 outer housing layers take the form of concentric tubes, and the integral means for heating the inner and outer housing layers comprises a heating wire coiled around either the inside or the outside of the outer housing layer.

12. The use of a membrane interface device according to any one of claims 1 to 9 or a 15 replaceable membrane cartridge according to claim 10 or claim 11 in an analytical process for detection of volatile and/or semivolatile organic compounds in a liquid or gas sample.

13. The use according to claim 12 comprising the steps of:: 20 1) achieving retention of analyses in the membrane; 2) drying the membrane with the use of an inert drying gas; 3) heating the membrane using the integral heating means.! 14. The use according to claim 12 or claim 13 which also comprises cooling the 25 membrane.

15. The use according to any one of claims 12-14 In which the membrane Is heated stepwise. 30 16. The use according to claim 12 which comprises achieving continuous permeation of the analyses through the membrane.