Mass spectrometer having variable sensitivity

Abstract

A mass spectrometer having an ionisation source 2, vacuum chamber 4 that is the first downstream of the ionisation source 2, an inlet 8 through a wall of the vacuum chamber, and an orifice varying mec

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority from and the benefit of United Kingdom patent application No. 2411576.8 filed on 6 August 2024. The entire contents of this application are incorporated herein by reference. FIELD OF THE INVENTION The present invention relates generally to mass spectrometry and in particular to a mass spectrometer having variable sensitivity. BACKGROUND Mass analysers are typically unable to operate at, or near, atmospheric pressure and so are required to be arranged within a vacuum chamber that is evacuated to a relatively low pressure before mass analysis can occur. Most mass analysers of this kind operate at a pressure of 10'4 mbar or lower. Mass spectrometers having atmospheric pressure ionisation (API) sources comprise an ionisation source that is outside of the vacuum system and therefore require a sampling orifice in a vacuum chamber in order to allow the ions from the ionisation source to enter the vacuum chamber. The most direct way to deliver ions to the mass analyser would be to provide a single vacuum chamber having the mass analyser therein, with a sampling orifice in the vacuum chamber for allowing ions to pass from the ionisation source to the mass analyser. However, in order to maintain the desired pressure in the vacuum chamber, either the sampling orifice has to be very small, which severely restricts the proportion of ions that can be transmitted through the orifice, or the vacuum pump used to maintain the vacuum in the vacuum chamber has to be impractically large. As such, mass spectrometers typically include a series of vacuum chambers that are interconnected by differential pumping apertures in order to progressively reduce the pressure in the downstream direction to that which is required by the mass analyser. In such an arrangement the pressure differential across the sampling orifice, and across each differential pumping aperture between vacuum chambers, is relatively small. As such, each of the sampling orifice and apertures is able to be relatively large, whilst still maintaining the required pressure differential across it and without having to use impractically large vacuum pumps. SUMMARY The present invention provides a mass spectrometer comprising: a vacuum chamber; an inlet through a wall of the vacuum chamber; and an orifice varying mechanism for providing an orifice at the inlet; wherein the mass spectrometer is operable in a first mode in which the orifice varying mechanism provides a relatively large orifice at the inlet such that ions pass therethrough, and in a second mode in which the orifice varying mechanism provides a smaller orifice at the inlet such that ions pass therethrough. The spectrometer may comprise an ionisation source upstream of the vacuum chamber, and the spectrometer may be configured to maintain the vacuum chamber at a lower pressure than the region in which the ionisation source is located. The orifice restricts the passage of ions and gas into the inlet. As such, the first mode may provide the spectrometer with a relatively high sensitivity since a relatively high proportion of ions travelling towards the inlet will be transmitted therethrough in that mode, whereas the second mode may provide the spectrometer with a lower sensitivity since a smaller proportion of ions travelling towards the inlet will be transmitted therethrough in that mode. The orifice varying mechanism may be configured so as to be manually switchable between the first and second modes, or the spectrometer may be configured to automatically switch between the first and second modes. The spectrometer may comprise control circuitry configured to control the orifice varying mechanism so as to switch between the first and second modes. The spectrometer may be configured to remain in each mode for at least 10 seconds. The spectrometer may comprise an ionisation source, wherein the vacuum chamber is the first vacuum chamber downstream of the ionisation source. The orifice may be a sampling orifice, e.g. located in a sampling cone. The ionisation source may be located in an atmospheric pressure region. It is contemplated that the orifice may alternatively be a differential pumping aperture in a wall between two vacuum chambers that are pumped down to two different respective pressures. The orifice varying mechanism may comprise one or more members having a first, relatively large orifice therein and a second, relatively smaller orifice therein; wherein the orifice varying mechanism is controllable to move the one or more members relative to said inlet so as to provide said first orifice at the inlet in said first mode and said second orifice at the inlet in the second mode. The size of each of the first and second orifices may be fixed. The one or more members may be moved relative to said inlet so that the axes through the first and second orifices move relative to the axis through the inlet. The orifice varying mechanism may be configured such that the first and second orifices are slidable relative to said inlet such that the first orifice is at the inlet in said first mode and said second orifice is at the inlet in the second mode. The orifice varying mechanism may be sealed over the inlet such that in the first mode gas may only be able to pass into the inlet and vacuum chamber through the first orifice, and in the second mode gas may only be able to pass into the inlet and vacuum chamber through the second orifice. The first orifice may be provided in a first sample cone and the second orifice may be provided in a second sample cone. The first and second sample cones may therefore be slidable relative to the inlet. Alternatively, the first and second orifices may be provided in one or more moveable member arranged between a sample cone and the inlet. The one or more movable member may be slidable relative to the inlet. The one or more movable member may be sealed relative to the sample cone and inlet such that in the first mode gas may only be able to pass from the sample cone into the inlet via the first orifice, and in the second mode gas may only be able to pass from the sample cone into the inlet via the second orifice. The orifice varying mechanism may be controllable to move the one or more moveable member between a first position in the first mode in which the first orifice is aligned with a bore through the sample cone and the axis through the inlet, and a second position in in the second mode in which the second orifice is aligned with the bore through the sample cone and the axis through the inlet. The one or more movable member may have a first bore therethrough that has the first orifice therein that restricts the passage of gas through the first bore, and a second bore therethrough that has the second orifice therein that restricts the passage of gas through the second bore. In the first mode the first bore may be aligned with the bore through the sample cone and the axis through the inlet, whereas in the second mode the second bore may be aligned with the bore through the sample cone and the axis through the inlet. The first bore may have a maximum diameter that is larger than the diameter of the first orifice and / or the second bore may have a maximum diameter that is larger than the diameter of the second orifice. Embodiments are contemplated in which the orifice varying mechanism comprises an iris mechanism having an aperture therethrough that is variable in size between said relatively large orifice in said first mode and said smaller orifice in said second mode. The orifice varying mechanism described herein may be biased to operate in the second mode in which the orifice varying mechanism provides the smaller orifice at the inlet. The biasing may be a mechanical biasing. For example, the orifice varying mechanism may comprise a resilient biasing member, such as a spring, to bias the mechanism to provide the smaller orifice at the inlet. The spectrometer described herein may comprise a vacuum system for evacuating gas from the vacuum chamber and control circuitry configured to control the vacuum system such that it maintains the pressure in the vacuum chamber at substantially the same pressure in both the first and second modes. The vacuum system may comprise a vacuum pump and the control circuitry is configured to control the vacuum pump to operate at a first pumping speed in the first mode and a second, lower pumping speed in the second mode. A pressure sensor may be provided in the vacuum chamber and the pressure measured by the pressure sensor may be used by the control circuitry to control the vacuum system so as to maintain the vacuum chamber at substantially the same pressure in both the first and second modes. Alternatively, the control circuitry may be configured to control the vacuum system to operate in a predetermined first way during the first mode (e.g. at a predetermined first speed) and in a predetermined second way during the second mode (e.g. at a predetermined second speed). In order to provide uniform performance in geographical locations that have different AC electrical power supplies, vacuum pumps include power converters that convert mains AC power into a predetermined AC frequency that is then used to drive the motor of the vacuum pump so that it has a certain pre-determined pumping speed. Embodiments of the present invention use this power converter to vary the gas pumping speed between the first and second modes. Accordingly, the vacuum pump may comprise a power converter configured to receive an AC electrical current from a mains electrical supply, change its frequency and then supply the AC electrical current to a motor that drives the vacuum pump, wherein said control circuitry is configured to control the power converter such that an AC electrical current having a first frequency is supplied to the motor in the first mode and an AC electrical current having a second, different frequency is supplied to the motor in the second mode. The vacuum system may comprise a vacuum pump and at least one conduit between the vacuum pump and the vacuum chamber for evacuating gas therethrough, wherein the control circuitry is configured to control the vacuum system so as to evacuate the vacuum chamber through a conduit having a gas passage therethrough that is relatively restricted in the second mode, and to evacuate the vacuum chamber through a conduit having a gas passage therethrough that is less restricted in the first mode. For example, the spectrometer may comprise a single conduit between the vacuum pump and the vacuum chamber that comprises a valve for controlling the gas flow rate through the conduit, and the control circuitry may be configured to control the valve to open by a first amount in the second mode and to open by a greater amount in the first mode. Alternatively, the spectrometer may comprise: a) a first conduit between the vacuum pump and the vacuum chamber that comprises a first valve, and a second, different conduit between the vacuum pump and the vacuum chamber that comprises a second valve; wherein the control circuitry is configured such that in the first mode the spectrometer opens the first valve whilst maintaining the second valve closed such that the vacuum pump evacuates the vacuum chamber through the first conduit, and in the second mode opens the second valve whilst maintaining the first valve closed such that the vacuum pump evacuates the vacuum chamber through the second conduit; wherein the second conduit provides a gas passage therethrough, when the second valve is open, that is relatively restricted and the first conduit provides a gas passage therethrough, when the first valve is open, that is less restricted; or b) a first conduit between the vacuum pump and the vacuum chamber that comprises a first valve, and a second, different conduit between the vacuum pump and the vacuum chamber that comprises a second valve; wherein the control circuitry is configured such that in the second mode the spectrometer opens the first valve whilst maintaining the second valve closed such that the vacuum pump evacuates the vacuum chamber through the first conduit, and in the first mode opens both the first and second valves such that the vacuum pump evacuates the vacuum chamber through both the first and second conduits. The spectrometer herein may comprise a further vacuum chamber downstream of said vacuum chamber, and a turbomolecular pump connected to the further vacuum chamber for evacuating the further vacuum chamber, wherein a gas inlet to said vacuum pump is connected to a gas exhaust from said turbomolecular pump. The present invention also provides a mass spectrometer comprising: a vacuum chamber; a first orifice in an upstream wall of the vacuum chamber for allowing ions therethrough; and a second, smaller orifice in the upstream wall of the vacuum chamber for allowing ions therethrough; wherein either: a) the mass spectrometer is configured to be operable in a first mode in which ions are transmitted through the first orifice but not the second orifice, and in a second mode in which ions are transmitted through the second orifice but not the first orifice; or b) the mass spectrometer is configured to transmit ions simultaneously through both the first and second orifices, and wherein the mass spectrometer is configured to be operable in a first mode in which ions that have passed through the first orifice, or ions derived therefrom, are transmitted to a mass analyser in the spectrometer, whereas ions that have passed through the second orifice are filtered out; and wherein the mass spectrometer is configured to be operable in a second mode in which ions that have passed through the second orifice, or ions derived therefrom, are transmitted to the mass analyser, whereas ions that have passed through the first orifice are filtered out. The present invention also provides a mass spectrometer comprising: a vacuum chamber; a first orifice in an upstream wall of the vacuum chamber for allowing ions therethrough; and a second orifice in the upstream wall of the vacuum chamber for allowing ions therethrough; wherein either: a) the mass spectrometer is configured to be operable in a first mode in which ions are simultaneously transmitted through both the first orifice and the second orifice, and in a second mode in which ions are transmitted through the first orifice but not the second orifice; or b) the mass spectrometer is configured to transmit ions simultaneously through both the first and second orifices, and wherein the mass spectrometer is configured to operable in: a first mode in which ions that have passed through both the first orifice and the second orifice, or ions derived therefrom, are transmitted to a mass analyser in the spectrometer; and in a second mode in which ions that have passed through the first orifice, or ions derived therefrom, are transmitted to the mass analyser, whereas ions that are that have passed through the second orifice are filtered out. It is contemplated that the sensitivity of the mass spectrometer may be varied between the first, relatively high sensitivity mode and the second, lower sensitivity mode using techniques other than those described above. For example, the sensitivity may be varied between the two modes by applying one or more different voltages to one or more electrodes within the mass spectrometer in the different modes, so as to vary the transmission of ions to the mass analyser. The frequency and / or amplitude of the one or more voltages may be varied so as to vary the sensitivity. For instance, ions may be driven through the mass spectrometer using different voltages in the different sensitivity modes. In one sensitivity mode a DC gradient may be used to drive ions through an ion guide and in another sensitivity mode voltages may be successively applied to successive electrodes of the ion guide so as to repeatedly travel potential barriers along the ion guide. Other factors also influence the transmission of ions from the ionisation source to the mass analyser within the mass spectrometer. For example, such factors include: the number of differential pumping regions and consequently the number of differential apertures, the type and configuration of the ion guides (e.g. quadrupole, hexapole, multipole, stacked-ring ion guides and their physical parameters such as the inscribed radius of the device), ion mobility or Time-of-Flight effects, configuration and gain of detectors and detector electronics etc. The mass spectrometer may be configured such that any one or combination of these factors may be varied in order to vary the sensitivity of the mass spectrometer in the different modes. Accordingly, more generally, the present invention provides a mass spectrometry system comprising: a mass spectrometer configured to be operable in a first, relatively high sensitivity mode and in a second, lower sensitivity mode; an input device for receiving an indication of a type of assay that a sample is to be analysed by; and control circuitry configured to control the mass spectrometer to automatically operate in the first mode or the second mode based on said indication of the type of assay that the sample is to be analysed by. The present invention also provides a clinical mass spectrometry system comprising a mass spectrometer as described herein. The present invention provides a mass spectrometry system comprising: a mass spectrometer as described above; a sample reader for reading identifiers on samples received at the system; and control circuitry configured to control the system to: i) automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader; ii) automatically determine which of the first and second modes the mass spectrometer is to be operated in when analysing a given one of the samples based on the type of assay that it has been determined as being required to be analysed by; and iii) in response to step ii), control the mass spectrometer to mass analyse said sample whilst operating in the determined mode. The mass spectrometry system is preferably a clinical mass spectrometry system. The apparatus may be provided with a computer memory that correlates different types of assay with their respective sensitivity modes (i.e. the first mode or second mode) that the mass spectrometer is required to be operated in when performing the assays. The apparatus may then automatically determine the type of assay that a given sample is required to be analysed by from information in the identifier associated with it, using the sample reader. The apparatus may automatically determine which of the first or second modes is required to perform this assay, from the information in the computer memory. The apparatus then controls the mass spectrometer to mass analyse the sample whilst operating in the determined first or second mode. For example, if the assay that is required to be performed on the sample is an assay that requires a high sensitivity mass spectrometer then the mass spectrometer is automatically controlled to operate in the first mode when it mass analyses this sample. In contrast, if the assay that is required to be performed on the sample is an assay that requires a relatively low sensitivity mass spectrometer then the mass spectrometer is automatically controlled to operate in the second mode when it mass analyses this sample. The present invention also provides a method of mass spectrometry that uses the mass spectrometer described herein. Accordingly, the present invention provides a method of mass spectrometry comprising: providing a mass spectrometer as described above; operating the mass spectrometer in the first mode whilst mass analysing ions; and operating the mass spectrometer in the second mode whilst mass analysing ions. The present invention also provides a method of mass spectrometry comprising: transmitting ions through an orifice into a vacuum chamber and towards a mass analyser in both a first mode and a second mode, wherein the orifice has a relatively large area in the first mode and a relatively small area in the second mode. The method comprises mass analysing ions transmitted through said orifice in the first mode, or ions derived therefrom; and mass analysing ions transmitted through said orifice in the second mode, or ions derived therefrom. BRIEF DESCRIPTION OF THE DRAWINGS Various embodiments of the present invention will now be described by way of example only and with reference to the accompanying drawings, in which: Fig. 1 shows a schematic of a known mass spectrometer; Fig. 2 shows a plot of the relative ion transmission through a mass spectrometer sampling orifice as a function of the diameter of the orifice; Fig. 3 shows a schematic of an embodiment of the present invention for varying the size of the sampling orifice into the first vacuum chamber of a mass spectrometer; Figs. 4A-4B and Figs. 5A-5B show sample cones that may be used in the embodiments of the present invention; Figs. 6A-6B show a sampling orifice varying mechanism according to an embodiment of the present invention that switches between two sample cones having sampling orifices of different sizes; Figs. 7A-7B show a sampling orifice varying mechanism according to another embodiment of the present invention that uses an iris aperture mechanism; Figs. 8A-8B show a sampling orifice varying mechanism according to another embodiment of the present invention that uses a single sample cone along with a sliding mechanism that switches between different sampling orifices; Fig. 9 shows a schematic of a mass spectrometer according to an embodiment of the present invention; Fig. 10 shows an embodiment in which two sample cones are arranged over two respective ion inlet apertures to the first vacuum chamber; and Fig. 11 shows a schematic of an automated clinical LC-MS system according to an embodiment of the present invention. DETAILED DESCRIPTION Fig. 1 shows a schematic of a known spectrometer for help in understanding the present invention. The spectrometer comprises an ion source enclosure 2 for enclosing an atmospheric pressure ionisation (API) source, a first vacuum chamber 4 and a second vacuum chamber 6. A sampling orifice 8 is provided in the upstream wall of the first vacuum chamber 4 so as to allow ions to enter the first chamber 8 from the ionisation source located in the ion source enclosure 2. A mass analyser (not shown) is arranged in the second vacuum chamber 6. A differential pumping aperture 10 is arranged in the wall between the first and second vacuum chambers such that the ions can pass from the first vacuum chamber 4 into the second vacuum chamber 6 and then into the mass analyser arranged therein. A roughing pump 12 is connected to the first vacuum chamber 4 for evacuating the first vacuum chamber 4. This pump reduces the pressure in the first vacuum chamber 4 to a pressure below atmospheric pressure. A turbomolecular pump 14 is connected to the second vacuum chamber 6 for evacuating the second vacuum chamber 6 to a pressure below that of the first vacuum chamber 4. It is typically desired to reduce the pressure in the second vacuum chamber 6 to a very low pressure in order for the mass analyser housed therein to operate optimally. It will be appreciated that reducing the pressure in the first vacuum chamber 4 using the roughing pump 12 enables the turbomolecular pump 14 to evacuate the second vacuum chamber 6 more easily, since the gas flow rate from the first vacuum chamber 4 into the second vacuum chamber 6 is lower. However, turbomolecular pumps are not able to efficiently pump gas from a vacuum chamber out to a region that is at atmospheric pressure. Accordingly, the roughing pump 12 is connected to the outlet 16 of the turbomolecular pump 14 so that the roughing pump 12 can pump the outlet 16 of the turbomolecular pump down to a pressure of a few millibars. This process is known in the art as the roughing pump (also known as a “backing pump”) backing the turbomolecular pump 14. In use, the ionisation source in the ion source enclosure 2 ionises an analytical sample so as to produce ions. The ions then pass from the relatively high pressure ion source enclosure 2, through the sampling orifice 8, and into the lower pressure first vacuum chamber 4. The ions are then guided through the first vacuum chamber 4 by an ion guide, through the differential pumping aperture 10, and into the lower pressure second vacuum chamber 6, wherein they are guided into the mass analyser. Even when multiple vacuum chambers are used to obtain the desired pressure in the mass analyser, the sensitivity of a mass spectrometer is closely coupled to the pumping speed of each vacuum pump, i.e. the volume flow rate that the pump is capable of displacing. Put simplistically, a vacuum pump having a higher pumping speed will allow the mass spectrometer to have larger orifices, whilst maintaining the same pressure in a given region, which allows a greater proportion of the ions to pass through the orifices and so increases the sensitivity of the mass spectrometer. In a conventional mass spectrometer having an API source, the gas throughput through the sampling orifice into the first vacuum chamber is typically approximately 100 to 10,000 standard cubic centimetres per minute. Fig. 2 shows an example of how the relative ion transmission through a sampling orifice varies as a function of diameter of the orifice in a single quadrupole mass spectrometer having an API source. In the experiment to obtain this data a valve was used to throttle the pumping of the first vacuum chamber so as to maintain the pressure in this region the same for each measurement. As can be seen from Fig. 2, a reduction in the diameter of the orifice from 0.5 mm to 0.15 mm results in the ion transmission being halved. The above-described issues also apply to other orifices in the mass spectrometer through which ions are transmitted, such as the differential pumping aperture 10 in Fig. 1. Typically, the orifice sizes are selected as a compromise between ion transmission (i.e. mass spectrometer sensitivity) and gas pumping requirements. However, the inventors have recognised that it can be desirable for a mass spectrometer to operate in one mode that has a relatively high sensitivity and in another mode that has a lower sensitivity. For example, such a mass spectrometer is useful in an automated clinical analyser, such as one that performs liquid chromatography mass spectrometry (LC-MS). LC-MS is often used within a clinical laboratory setting to determine concentrations or quantities of various clinically relevant molecules in a biological patient sample, such as blood, blood plasma, blood serum, urine, stool, saliva, or cerebrospinal fluid. LC-MS is often referred to as the ‘gold standard’ and has become the accepted reference method for a variety of analytes due to its high sensitivity and specificity, and wide dynamic range. Examples of typical analytes that can be detected or quantified by LC-MS systems include steroid hormones, vitamins, ‘drugs of abuse’ such as opiates, and therapeutic drugs such as immunosuppressants. There is also growing interest in peptide and protein analyses, particularly in the fields of oncology and neurology, as potential indicators of disease or disorder. As LC-MS technology is yet to be fully automated in the way that clinical chemistry, immunoassay and PCR technologies have been automated, it is typical for LC-MS systems to be physically located in a separate laboratory to the other systems, which are located in the core laboratory. As such, LC-MS systems are typically operated with highly trained and educated staff which, combined with the manual nature of the analysis techniques, leads to high costs per sample test. There is a desire within the industry to provide automated LC-MS systems suitable for deployment within the core laboratory and capable of being operated by lower skilled staff. Such automated analysers require a high level of robustness and reliability, both of which maximise uptime and hence help to reduce costs. An important aspect in determining the success of a fully automated LC-MS clinical analyser is the size of the menu of tests that the analyser is capable of performing, and regulatory-cleared tests being available. To maximise the breadth of the menu it is desirable to have a high sensitivity mass spectrometer. For example, tests with low sample volumes such as those using dry blood spot samples, or tests for low level endogenous compounds such as aldosterone, require a highly sensitive mass spectrometer. However, the majority of tests that are currently performed routinely do not require such high levels of sensitivity. The straight-forward solution to designing a single mass spectrometer that can cover the range of sensitivity needs for a broad clinical menu is therefore to design one with a high level of sensitivity. However, this neglects several important considerations. Firstly, as discussed above, important aspects in determining the sensitivity of a mass spectrometer are the sizes of the sampling orifice and differential pumping apertures, and the available pumping speed of the vacuum pumps. A sensitive instrument having a high ion transmission level would draw in a significant quantity of ions of the analyte of interest, but it would also draw in substantial unwanted materials such as ions of other analytes and neutral molecules of other species present in the sample such as components of the sample matrix. Both the ions and neutral molecules can contaminate the inner surfaces of the mass spectrometer, including the various orifices and ion guides described above, which degrades the performance of the mass spectrometer over time. For example, ions or neutral species can impact on the electrodes of an ion guide and form a layer that alters the electric fields within the ion guide to an extent that impedes the transmission of ions. Even if the layer itself does not affect ion transmission, ions may impact on the layer and cause charge to build up thereon, which may negatively affect the transmission of ions. Similarly, ions that are not desired to be transmitted may be filtered out or otherwise end up striking apertures or electrodes, again causing contamination as described above Also, if a sample having a high concentration of an analyte is analysed on a sensitive mass spectrometer, the ion detector may become saturated. Also, the relatively large gas loads associated with higher sensitivity mass spectrometers having large apertures require a relatively high power consumption for the vacuum pumps, as work is done to evacuate the gas from the vacuum chambers. This higher level of power consumption by the pumps, plus the increased power consumed by the laboratory air conditioning system to remove the additional heat generated by the pumps, are important ecological and economic considerations. Such pumps and air conditioning systems also generate a relatively large amount of noise. The inventors have recognised that it is desirable to have a single mass spectrometer that in one mode of operation has a high sensitivity and in another mode of operation has a lower sensitivity. The sensitivity of the mass spectrometer may be varied by varying the size of an aperture through which the ions are required to be transmitted, such that when the aperture is relatively large the proportion of ions transmitted through the aperture is relatively high (i.e. a high sensitivity mode) and when the aperture is smaller the proportion of ions transmitted through the aperture is lower (i.e. a lower sensitivity mode). Fig. 3 shows a schematic of an embodiment of the present invention for varying the size of the sampling orifice into the first vacuum chamber 4 of the mass spectrometer. The mass spectrometer may be of the form shown in Fig. 1, or any other form. A vacuum pump 12 is provided for evacuating the first vacuum chamber 4 through a wall thereof, via a first vacuum hose 16. This vacuum pump 12 may also pump down the exhaust of the turbomolecular pump 14 via a second vacuum hose 18, e.g. in the manner described in relation to Fig. 1. A sampling orifice varying mechanism 20 is provided for varying the size of the sampling orifice that allows ions to pass from the ionisation source into the first vacuum chamber 4. This mechanism 20 may be controlled by an electronic controller 22, so that the mechanism 20 varies the size of the sampling orifice that allows ions into the first vacuum chamber 4. The controller 22 may also control the vacuum pump 12 in a manner that is dependent on the size of the sampling orifice being used to allow ions into the first vacuum chamber, as will be described below. Varying the size of the sampling orifice that allows ions into the first vacuum chamber 4 causes a variation in the gas flow passing through the orifice 8. The inventors have recognised that it is advantageous to provide a concomitant variation in the speed at which the vacuum pump 12 pumps gas out of the first vacuum chamber 4 such that the pressure in the first vacuum chamber remains substantially the same when the size of the sampling orifice 8 is changed. For example, the controller 22 may control the vacuum pump 12 so as to vary the pumping speed of the pump such that the pressure in the first vacuum chamber remains substantially the same. It is important to maintain the pressure in the first vacuum chamber substantially the same for multiple reasons. For example, maintaining the pressure in the first vacuum chamber at the same level means that there is consistent gas flow into and through downstream vacuum chambers and hence the pressures in those downstream vacuum chambers are also maintained substantially constant. Maintaining the pressures constant enables the level of ion cooling due to the ions colliding with background gas to remain constant, which helps maintain the level of ion transmission and mass resolution of the mass analyser constant. Also, as it is common to monitor the pressure levels in vacuum chambers to determine if there is a fault such as a vacuum leak, it is desirable to avoid varying the pressure during operation. It is also desirable to maintain the pressure constant so as to avoid being restricted to using different voltages. More specifically, different pressure regimes require different restrictions on the voltages that may be used in those regimes in order to avoid electrical breakdown, i.e. electrical arcing. Also, as the same vacuum pump may be used to pump the first vacuum chamber and to pump down the outlet of the turbomolecular pump, a change in pressure in the first vacuum chamber would result in a corresponding change in the pressure at the exhaust of the turbomolecular pump changing. If the pressures in the first vacuum chamber and at the exhaust of the turbomolecular pump increased, then this would increase the power consumed by the turbomolecular pump and thereby increase the heat generated by this pump. This could cause the turbomolecular pump to overheat. On the other hand, if the pressures in the first vacuum chamber and at the exhaust of the turbomolecular pump decreased, then the power consumed by the turbomolecular pump and the heat generated thereby would decrease. Whilst this is beneficial from a power consumption perspective, the decrease in heat output from the turbomolecular pump may also reduce the temperature of other parts of the mass spectrometer that are in close thermal proximity, which can impact the stability of performance of the mass spectrometer. The sampling orifice varying mechanism disclosed herein varies the size of the sampling orifice that allows ions into the first vacuum chamber. For example, the sampling orifice varying mechanism may comprise multiple sampling orifices that have different respective sizes, and it may switch between using different sampling orifices to allow ions to enter the vacuum chamber. Each sampling orifice may be provided in a sample cone that covers an inlet aperture in a wall of the first vacuum chamber. Figs. 4A-4B and Figs. 5A-5B show sample cones that may be used in the sampling orifice varying mechanism. Fig. 4A shows a perspective view of a sample cone 24, and Fig. 4B shows a cross-sectional view through the sample cone. The orifice at the apex of the cone is the sampling orifice 8 that limits the passage of ions into the first vacuum chamber 4. Fig. 5A shows a perspective view of another sample cone 24, and Fig. 5B shows a cross-sectional view through the sample cone. In this sample cone the sampling orifice 8 that limits the passage of ions into the first vacuum chamber is located within the body of the sample cone. Figs. 6A-6B show a sampling orifice varying mechanism 20 according to an embodiment of the present invention. The mechanism comprises two different sample cones 24a,24b of the type shown in Figs. 4A-4B, where the different sample cones have differently sized sampling orifices 8. More specifically, the upper sample cone 24b has a relatively small sampling orifice 8 and the lower sample cone 24a has a larger sampling orifice 8. The two cones are mounted on a sliding mechanism such that the cones may be moved relative to an inlet aperture 26 in the wall of the first vacuum chamber 4. When it is desired for the mass spectrometer to have a relatively high sensitivity, the sliding mechanism is moved to the position shown in Fig. 6A such that the sample cone 24a having the larger sampling orifice is located over the inlet aperture 26. This enables a relatively high ion transmission level through the sample cone and into the first vacuum chamber 4. In contrast, when it is desired for the mass spectrometer to have a relatively low sensitivity, the sliding mechanism is moved to the position shown in Fig. 6B such that the sample cone 24b having the smaller sampling orifice is located over the inlet aperture. This only enables a relatively low ion transmission level through the sample cone and into the first vacuum chamber. It will be appreciated that the cross-sectional area of the largest sampling orifice is the same or smaller than the cross-sectional area of the inlet aperture. The sampling orifice varying mechanism 20 may be configured such that gas is only able to pass into the inlet aperture 26 of the first vacuum chamber 4 through the sampling orifices in the sample cones 24a,24b. In other words, the sliding mechanism may be sealed about the inlet aperture in order to achieve this. Although the embodiment illustrates sample cones of the form shown in Figs. 4A-4B, it will be appreciated that one or both of the sampling orifices may be provided in a component having a different form, such as one or both of the sample cones being of the form shown in Figs. 5A-5B. However, the different sized sampling orifices may be provided in components having different forms to those shown. Additionally, or alternatively, although the embodiment illustrated only has two different sized sampling orifices, it is contemplated that more than two differently sized sampling orifices may be provided and the sliding mechanism may move these such that any one of these sampling orifices can be located over the inlet aperture to the first vacuum chamber. Figs. 7A-7B show a sampling orifice varying mechanism 20 according to another embodiment of the present invention. In this embodiment an iris aperture mechanism is sealed over, or in, the inlet aperture 26 to the first vacuum chamber 4. This mechanism has an aperture through it that serves at the sampling orifice 8, and is controllable so as to vary the cross-sectional area of the aperture. As is well known in iris mechanisms, the components of the iris mechanism that surround the aperture are movable relative to each other so as to vary the size of the aperture. When it is desired for the mass spectrometer to have a relatively high sensitivity, the iris aperture mechanism is controlled so as to enlarge the aperture 8 therethrough, as shown in Fig. 7A. This enables a relatively high ion transmission level through the iris aperture and into the first vacuum chamber. In contrast, when it is desired for the mass spectrometer to have a relatively low sensitivity, the iris aperture mechanism is controlled so as to decrease the size of the aperture therethrough, as shown in Fig. 7B. This only enables a relatively low ion transmission level through the iris aperture and into the first vacuum chamber. Although the iris aperture is shows as having two different sizes, the iris aperture mechanism may be controlled so that the aperture therethrough has more that two different sizes so as to provide the mass spectrometer with more than two respective sensitivities. It will be appreciated that the iris aperture is controllable to have multiple different cross-sectional areas, where at least one of these areas is smaller than the cross-sectional area of the inlet aperture to the first vacuum chamber. The iris mechanism may be configured such that gas is only able to pass into the inlet aperture of the first vacuum chamber through the sampling iris aperture. Figs. 8A-8B show another embodiment that is similar to that in Figs. 6A-6B, except that rather than using a sliding mechanism that switches between two different sample cones, a single sample cone 24 is used along with a sliding mechanism 20 that switches between different sampling orifices 30a,30b. In this embodiment the bore 28 through the sample cone is aligned with the inlet aperture 26 of the first vacuum chamber 4. The sliding mechanism is provided between the bore 28 of the sampling cone 24 and the inlet aperture 26, where the sliding mechanism includes two bores 32a,32b that have differently sized apertures 30a,30b therein that restrict the gas flow through their respective bores. In the illustrated embodiment, the upper bore 32a has a relatively large diameter sampling orifice 30a therein and the lower bore 32b has a smaller sampling orifice 30b therein. For example, the larger sampling orifice 30a may have a diameter of 0.9 mm and the smaller sampling orifice 30b may have a diameter of 0.4 mm. This sliding mechanism is sealed, such as by seals 34, such that gas is only able to pass into the inlet aperture 26 of the first vacuum chamber via the bore 28 in the sample cone 24 and one of the bores 32a,32b of the sliding mechanism that is aligned with the inlet aperture and the bore in the sample cone. As such, the sliding mechanism may be moved so as to select which bore 32a,32b, and hence which sampling orifice 30a,30b, limits the gas flow into the inlet aperture 26 of the first vacuum chamber. The sliding mechanism may be biased such that one of the bores is aligned with the inlet aperture, e.g. by a resilient biasing member such as a spring 36. As shown more clearly in Fig. 8B, the bores 32a,32b and sampling orifices 30a,30b may be provided in a cylindrical member 38 that is slidable relative to the inlet aperture 26. When it is desired for the mass spectrometer to have a relatively high sensitivity, the sliding mechanism is moved such that the larger sampling orifice 30a is aligned with the inlet aperture 26. This enables a relatively high ion transmission level through it and into the first vacuum chamber. In contrast, when it is desired for the mass spectrometer to have a relatively low sensitivity, the sliding mechanism is moved such that the smaller sampling orifice 30b is aligned with the inlet aperture 26, as shown in Figs. 8A-8B. This only enables a relatively low ion transmission level into the first vacuum chamber. It will be appreciated that the cross-sectional area of the largest sampling orifice 30a is the same or smaller than the cross-sectional area of the inlet aperture 26. Although the embodiment illustrated has only two differently sized sampling orifices, it is contemplated that more than two differently sized sampling orifices may be provided and the sliding mechanism may move these such that any one of these sampling orifices can be aligned with the inlet aperture to the first vacuum chamber. As described above, embodiments of the present invention maintain a substantially constant pressure in the first vacuum chamber 4 when the mass spectrometer operates in the different sensitivity modes. This may be achieved by varying the pumping speed of the vacuum pump 12 that evacuates the first vacuum chamber. The vacuum pump may be an oil-sealed rotary or rotary-vane pump, a roots pump, an orbital scroll pump, a diaphragm pump, a claw pump or a screw pump. The electrical motors in vacuum pumps are conventionally directly driven by a mains AC electrical supply. In order to provide uniform performance in geographical locations that have different electrical power supplies, such as different frequency AC power supplies, such pumps include variable-frequency drives that convert the mains power into a predetermined frequency that is then used to drive the vacuum pump at a certain pumping speed. Embodiments of the present invention use this variable-frequency drive to vary the gas pumping speed when the gas load into the first vacuum chamber varies. More specifically, when the mass spectrometer is switched to operate in the relatively high sensitivity mode by using a relatively large sampling orifice, the gas load into the first vacuum chamber is relatively high and so the vacuum pump is controlled so as to have a relatively high pumping speed. In contrast, when the mass spectrometer is switched to operate in the lower sensitivity mode by using a smaller sampling orifice, the gas load into the first vacuum chamber is lower and so the vacuum pump is controlled so as to have a lower high pumping speed. The mass spectrometer may be switched between the different sensitivity modes manually or automatically. For example, both the size of the sampling orifice and the pumping speed of the vacuum pump may be varied manually, or both varied automatically (either simultaneously or in a synchronised manner). Alternatively, the size of the sampling orifice may be varied manually and the pumping speed of the vacuum pump varied automatically. Alternatively, the size of the sampling orifice may be varied automatically and the pumping speed of the vacuum pump controlled manually. Although embodiments have been described in which the pressure in the first vacuum chamber is maintained substantially constant during the different sensitivity modes by varying the pumping speed of a vacuum pump, it is contemplated that the pressure may be maintained constant in other ways, e.g. as will be described in relation to Fig. 9 Fig. 9 shows an embodiment of a mass spectrometer that is the same as that shown in Fig. 1, except that the vacuum pump 12 is connected to the first vacuum chamber 4 by two different conduits 40a,40b, each for pumping down the first vacuum chamber 4. Each of the conduits 40a,40b has a pump valve 42a,42b therein, which is selectively openable and closable so as to selectively open and close the conduits 40a,40b between the vacuum pump 12 and the first vacuum chamber 4. The first pump valve 42a in the first conduit 40a is configured to restrict the gas flow therethrough, when the first pump valve is open, by a greater amount than the second pump valve 42b in the second conduit 40b restricts the gas flow therethrough, when the second pump valve is open (assuming the same pressure differential across the first and second conduits). For example, each of the pump valves 42a,42b may open and close an aperture in its respective conduit 40a,40b, wherein the aperture controlled by the first pump valve 40a has a smaller area than the aperture controlled by the second pump valve 40b. In the low sensitivity mode, when a relatively small sampling orifice admits ions into the vacuum chamber 4, the first pump valve 42a is maintained open and the second pump valve 42b is maintained closed. This provides a relatively restricted gas flow path from the first vacuum chamber 4 to the first gas pump 12 via the first conduit 40a so that gas is evacuated from the vacuum chamber at a relatively low rate. In contrast, in the higher sensitivity mode, when a larger sampling orifice admits ions into the vacuum chamber, the controller 22 causes control circuitry to close the first pump valve 42a so as to prevent gas flow through the first conduit 40a and opens the second pump valve 42b as to allow gas flow through the second conduit 40b. The second conduit 40b provides a relatively less restrictive gas flow path from the vacuum chamber 4 to the pump 12, so that gas is evacuated from the vacuum chamber 4 at a higher rate. Alternatively, rather than using a single conduit 40a,40b to evacuate the first vacuum chamber 4 in each of the two modes, it is contemplated that in the high sensitivity mode more conduits may be used to evacuate the first vacuum chamber than are used to evacuate the first vacuum chamber in the lower sensitivity mode, such that the combined higher gas flow rate through the conduits in the high sensitivity mode is greater than the gas flow rate through the conduit(s) in the lower sensitivity mode. For example, referring to Fig. 9, both conduits 40a,40b may evacuate gas from the first vacuum chamber 4 in the high sensitivity mode, whereas only one conduit may evacuate gas from the first vacuum chamber in the lower sensitivity mode. In this embodiment, the two conduits may restrict the gas flow by the same amount or different amounts. Although an embodiment has been described having two conduits 40a,40b for enabling the first pump 12 to evacuate the first vacuum chamber 4 at different rates, it is contemplated that only a single conduit may be provided between the pump 12 and the first vacuum chamber 4 for evacuating the first vacuum chamber. In this embodiment the conduit may have a variable pump valve located therein that is configured to be operable in the low sensitivity mode in which the pump valve provides a relatively great restriction to a gas flow through the conduit, and to be operable in the higher sensitivity mode in which the pump valve provides a lesser restriction to a gas flow through the conduit. For example, in the low sensitivity mode the pump valve may initially provide a relatively small aperture in the conduit for gas to flow through and may be operated so that in the higher sensitivity mode the pump valve provides a larger aperture in the conduit for gas to flow though. Although embodiments have been described in which the sensitivity of the mass spectrometer is varied by varying the size of the sampling orifice, it is contemplated that the size of a differential pumping aperture in the wall between two adjacent vacuum chambers of the mass spectrometer may be varied instead, or as well. The pressure in the downstream one of these two vacuum chambers may be maintained substantially constant in the different sensitivity modes, using a technique corresponding to that described above in relation to maintaining the first vacuum chamber at a substantially constant pressure. Although embodiments have been described in which the size of the sampling orifice is varied so as to vary the sensitivity of the mass spectrometer, the present invention contemplates other techniques for varying the sensitivity of the mass spectrometer, e.g. as shown in Fig. 10. Fig. 10 shows an embodiment in which two sample cones 24a,24b are arranged over two respective ion inlet apertures 26a,26b to the first vacuum chamber 4, although it will be appreciated that the two sample cones may be sealed over a single relatively large ion inlet aperture to the first vacuum chamber such that ions are able to pass into the vacuum chamber through both sample cones. One or more ion guide or ion funnel may be provided in the vacuum chamber for guiding ions that pass through either one, or both, of the sample cones towards the mass analyser. The ionisation source may be arranged such that ions are directed into and through both sample cones. In a low sensitivity mode, the mass spectrometer may be controlled such that only ions that pass through a first of the sample cones are permitted to pass downstream of the first vacuum chamber, e.g. by controlling the voltages that are applied to the one or more ion guides. In a higher sensitivity mode, the mass spectrometer may be controlled such that only ions that pass through the second of the sample cones are permitted to pass downstream of the first vacuum chamber (e.g. by controlling the voltages that are applied to the one or more ion guides), where the second sample cone has a larger sampling orifice 8 than the first sample cone. Alternatively, in the higher sensitivity mode, the mass spectrometer may be controlled such that ions that pass through both the first and second sample cones are permitted to pass downstream of the first vacuum chamber, e.g. by controlling the voltages that are applied to the one or more ion guides). In this embodiment, the first and second sample cones may have the same or different sized sampling orifices. Alternatively, the mass spectrometer may be configured to vary the way in which the ions are directed to the sample cones in order to vary the sensitivity of the spectrometer. For example, in a low sensitivity mode, the mass spectrometer may be controlled such that ions are directed from the ionisation source into only a first of the sample cones. In a higher sensitivity mode, the mass spectrometer may be controlled such that ions are directed from the ionisation source into only the second sample cone, where the second sample cone has a larger sampling orifice than the first sample cone. Alternatively, in the higher sensitivity mode, the mass spectrometer may be controlled such that ions are directed from the ionisation source into both the first and second sample cones. In this embodiment, the first and second sample cones may have the same or different sized sampling orifices. The ions may be directed as required by the various modes described above using electric fields. Alternatively, the ionisation source may be moved relative to the sample cones in order to direct the ions as described above. In other words, in the low sensitivity mode the ionisation source may be located in a first position or orientation, whereas in the higher sensitivity mode the ionisation source may be located in a second, different first position or orientation. Alternative embodiments are contemplated having separate ionisation sources for the different sampling cones. In the low sensitivity mode, the mass spectrometer may be controlled such that the analytical sample is only supplied to a first of the ionisation sources, which only directs ions through a first of the sample cones. In the higher sensitivity mode, the mass spectrometer may be controlled such that the analytical sample is only supplied to a second of the ionisation sources, which only directs ions through a second of the sample cones, where the second sample cone has a larger sampling orifice than the first sample cone. Alternatively, in the higher sensitivity mode, the mass spectrometer may be controlled such that the analytical sample is supplied to both the first and second ionisation sources, which direct ions through both the first and second sample cones. In this embodiment, the first and second sample cones may have the same or different sized sampling orifices. Although the present invention has been described with reference to various 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. For example, although only two vacuum chambers 4,6 downstream of the ion source enclosure 2 are shown and described above, it will be appreciated that one or more further vacuum chambers may be provided downstream of the ion source enclosure 2. For example, one or more further vacuum chamber may be arranged between the first and second vacuum chambers 4,6, with differential pumping apertures in the walls between adjacent chambers so as to allow ions to pass through all of the vacuum chambers. These additional vacuum chambers may be at different pressures to the first and second vacuum chambers, such as at pressures intermediate those of the first and second vacuum chambers. These additional vacuum chambers may be pumped down by the second vacuum pump 14 or by one or more other vacuum pump. It is also contemplated that the ionisation source may be in a vacuum chamber that is maintained at a pressure below atmospheric pressure. Although embodiments have been described in which the size of an orifice is varied in order to change the sensitivity (i.e. ion transmission level) of the mass spectrometer, it is contemplated that other means may be used to vary the sensitivity. For example, the sensitivity may be varied by varying one or more voltages that are applied to one or more electrodes within the mass spectrometer so as to vary the transmission of ions to the mass analyser. For example, the frequency and / or amplitude of the one or more voltages may be varied so as to vary the sensitivity. For instance, ions may be driven through the mass spectrometer using different voltages in the different sensitivity modes. For instance, in one sensitivity mode a DC gradient may be used to drive ions through an ion guide and in another sensitivity mode voltages may be successively applied to successive electrodes of the ion guide so as to repeatedly travel potential barriers along the ion guide. It is also well known that there are many other factors that influence the transmission of ions from the ion source to the mass analyser within the mass spectrometer. For example, such factors include: the number of differential pumping regions and consequently the number of differential apertures, the type and configuration of the ion guides (e.g. quadrupole, hexapole, multipole, stacked-ring ion guides and their physical parameters such as the inscribed radius of the device), ion mobility or Time-of-Flight effects, configuration and gain of detectors and detector electronics etc. Any one or combination of these factors may be varied in order to vary the sensitivity of the mass spectrometer. Embodiments have been described in which the sensitivity of the mass spectrometer is varied between different levels, e.g. by varying the size of the sampling orifice that allows ions into the vacuum chamber. It is contemplated that the sensitivity of the mass spectrometer may be varied automatically in response to an input that is indicative of the analyte being analysed for. Additionally, or alternatively, the manner in which the vacuum chamber is pumped (e.g. the speed of the pump or number of pumping conduits used) may be varied automatically in response to an input that is indicative of the analyte being analysed for. Such an embodiment is described below with reference to Fig. 11 Fig. 11 shows schematically an automated clinical LC-MS system according to an embodiment of the present invention. The system is operable to automatically perform different analytical tests, i.e. assays, on different samples that may be selected from a predefined menu of assays. Fig. 11 shows the main elements of the system, but it will be appreciated that there may be other elements of the system that are not illustrated. The system includes a number of processing stages which operate automatically under the control of controller 50 to perform respective processing steps for samples 52 being analysed. The processing modules may be arranged to form a pipeline, with an output of one processing module being an input to the next processing module, and with samples being passed between processing modules by appropriate interfaces, e.g. automatically under the control of controller 50. Each processing module may be configured by the controller to perform appropriate processing steps on a sample for an assay (i.e. analytical test) that the sample is undergoing. As shown in Fig. 11, the system may include a sample batcher module 54 that may be interfaced to a sample preparation module 56 by interface 58. Sample batcher module 54 receives samples 52, either individually or in groups. The sample batcher module temporarily buffers the received samples and outputs batches of samples that are to be processed by a downstream processing module of the system, such as the sample preparation module 56 and / or an LC module 58 and / or mass spectrometer module 60. The sample batcher module 54 may thus output samples in a different order to the order in which samples were received. The sample preparation module 56 receives the batch of samples from the sample batcher module 54, e.g. via interface 58, and prepares the samples for LC-MS analysis. The sample preparation module may prepare different samples sequentially at different times and / or in parallel at the same time. The sample preparation steps used may include any one, or any combination of any number of the following steps:- sample pipetting, aliquoting, addition of solvent, addition of one or more reagents, addition of one or more internal standards, addition of one or more quality controls, addition of one or more calibrators, addition of magnetic beads (with or without a functionalised coating for binding an analyte of interest), magnetic bead processing, sample reacting / incubating, solid phase extraction, protein precipitation, enzymatic digestion, filtration, centrifugation, shaking / mixing, heating, etc. LC module 58 receives the samples from sample preparation module 56, e.g. via interface 62, and separates each of the samples according to chromatographic retention in an LC separation column. The LC module may separate different samples sequentially, e.g. using the same column, and / or in parallel, e.g. using different columns. The LC module may comprise one or more sample injection systems, one or more pumping systems, one or more separation columns, one or more mobile phases, etc. The LC module may also be capable of flow injection. The LC module may have multiple different separation configurations available, e.g. such that it can use different column types, different mobile phase types, etc., and an appropriate configuration for a given sample may be selected by controller 50 based on the assay that is being performed. The MS module 60 mass analyses a given sample, after it has been prepared in sample preparation module 56 and separated in LC module 58, in order to detect and optionally quantify one or more analyte of interest in the sample. The LC module 58 may be interfaced with the MS module 60 via interface 64. The MS module outputs analysis data 66. The output data 66 may be indicative of whether one or more analytes of interest have been detected in a given sample and optionally the quantity or concentration of such analytes of interest. For example, it may be indicated whether the quantity or concentration of an analyte of interest is above or below a defined threshold, for example. The MS module has one or more ionisation source for ionising the eluant from the LC module and one or more mass spectrometers for mass analysing the ions produced therefrom. Interfaces 58, 62 and 64 may be provided between adjacent modules in order to transfer the samples between them. The interfaces may comprise one or more of an electro-mechanical assembly, track system, robotic system, fluidic connection, etc. Each interface may be controlled to transfer the samples automatically, or one or more of the interfaces may be performed manually by an operator. Each of the one or more mass spectrometers in module 60 is controllable to operate in multiple different sensitivity modes, e.g. as described in the above embodiments. The controller 50 may automatically select one of these modes for any given sample 52 being mass analysed based on the assay that is required to be performed on that sample. For example, when the apparatus receives a sample 52, it may automatically identify the assay that is to be performed on that sample, e.g. by reading a barcode provided on the sample container or some other identifier on the container (e.g. an RF ID tag). The mass spectrometer may then be automatically controlled to operate in a particular sensitivity mode based on the assay that has been identified as being required to be performed on that sample. More specifically, if the assay that is required to be performed on the sample is an assay that requires a high sensitivity mass spectrometer then the mass spectrometer is automatically controlled to operate in a relatively high sensitivity mode when it mass analyses this sample. In contrast, if the assay that is required to be performed on the sample is an assay that requires a relatively low sensitivity mass spectrometer then the mass spectrometer is automatically controlled to operate in a relatively low sensitivity mode when it mass analyses this sample. The apparatus may be provided with a computer memory that correlates different types of assay with the sensitivity of the mass spectrometer that is required to mass analyse them, and the apparatus may use this memory when performing the above process. By way of example, the mass spectrometer may be a tandem (MS / MS) mass spectrometer that monitors certain multiple reaction monitoring (MRM) transitions and produces an ion chromatogram for each of these, i.e. records the detected ion signal as a function of time. For each of the analytical samples the mass spectrometer may monitor an MRM transition for the analyte of interest required by the assay that it is undergoing. As one skilled in the art will appreciate, in order to monitor any given MRM transition the mass spectrometer controls a first mass filter to have a mass transmission window such that it is only capable of transmitting precursor ions having a specific mass to charge ratio. The precursor ions that are transmitted by the first mass filter are guided into a fragmentation or reaction device, in which the precursor ions are fragmented or reacted so as to form fragment or product ion species. The fragment or product ions are then transmitted to a second mass filter, which is operated so as to have a mass transmission window such that it is only capable of transmitting ions having a specific mass to charge ratio to an ion detector. The mass to charge ratio values of the mass transmission windows for the first and second mass filters are selected so that if ions are detected by the ion detector then it is determined that ions of interest are present in the sample being analysed. The ion signal may also be used to determine the quantity of ions in the sample. For the MRM transition for the analyte of interest, the mass to charge ratio values of the mass transmission windows for the first and second mass filters are selected so that only ions having a mass to charge ratio corresponding to a specific fragment ion species of the analyte of interest are able to be detected by the ion detector. The ion signal for these ions may therefore be used to determine the presence, and optionally quantity or concentration, of the analyte of interest in the sample. A different MRM transition for the analyte of interest may also be monitored, wherein the mass to charge ratio values of the mass transmission windows for the first and second mass filters are selected so that only ions having a mass to charge ratio corresponding to a different fragment ion species of the analyte of interest are able to be detected by the ion detector. The mass spectrometer may monitor this MRM transition so that if ions are detected for this MRM transition then it is confirmed that it is actually the analyte of interest that is being detected, since it is highly unlikely that a precursor ion other than the analyte of interest would give rise to ion signals for both MRM transitions.

Claims

1. A mass spectrometer comprising:an ionisation source;a vacuum chamber that is the first vacuum chamber downstream of the ionisation source;an inlet through a wall of the vacuum chamber; andan orifice varying mechanism for providing an orifice at the inlet;wherein the mass spectrometer is operable in a first mode in which the orifice varying mechanism provides a relatively large orifice at the inlet such that ions pass therethrough, and in a second mode in which the orifice varying mechanism provides a smaller orifice at the inlet such that ions pass therethrough.

2. The spectrometer of claim 1, comprising control circuitry configured to control the orifice varying mechanism so as to switch between the first and second modes.

3. The spectrometer of claim 1 or 2, wherein the orifice varying mechanism comprises one or more members having a first, relatively large orifice therein and a second, relatively smaller orifice therein; wherein the orifice varying mechanism is controllable to move the one or more members relative to said inlet so as to provide said first orifice at the inlet in said first mode and said second orifice at the inlet in the second mode.

4. The spectrometer of claim 3, wherein the orifice varying mechanism is configured such that the first and second orifices are slidable relative to said inlet such that the first orifice is at the inlet in said first mode and said second orifice is at the inlet in the second mode.

5. The spectrometer of claim 3 or 4, wherein the first orifice is provided in a first sample cone and the second orifice is provided in a second sample cone.

6. The spectrometer of claim 3 or 4, wherein the first and second orifices are provided in one or more moveable member arranged between a sample cone and the inlet.

7. The spectrometer of claim 6, wherein the orifice varying mechanism is controllable to move the one or more moveable member between a first position in the first mode in which the first orifice is aligned with a bore through the sample cone and the axis through the inlet, and a second position in in the second mode in which the second orifice is aligned with the bore through the sample cone and the axis through the inlet.

8. The spectrometer of claim 1 or 2, wherein the orifice varying mechanism comprises an iris mechanism having an aperture therethrough that is variable in size between said relatively large orifice in said first mode and said smaller orifice in said second mode.

9. The spectrometer of any preceding claim, wherein the orifice varying mechanism is biased to operate in the second mode in which the orifice varying mechanism provides the smaller orifice at the inlet.

10. The spectrometer of any preceding claim, comprising a vacuum system for evacuating gas from the vacuum chamber and control circuitry configured to control the vacuum system such that it maintains the pressure in the vacuum chamber at substantially the same pressure in both the first and second modes.

11. The spectrometer of claim 10, wherein the vacuum system comprises a vacuum pump and the control circuitry is configured to control the vacuum pump to operate at a first pumping speed in the first mode and a second, lower pumping speed in the second mode.

12. The spectrometer of claim 11, wherein the vacuum pump comprises a power converter configured to receive an AC electrical current from a mains electrical supply, change its frequency and then supply the AC electrical current to a motor that drives the vacuum pump, wherein said control circuitry is configured to control the power converter such that an AC electrical current having a firstfrequency is supplied to the motor in the first mode and an AC electrical current having a second, different frequency is supplied to the motor in the second mode.

13. The spectrometer of claim 10, 11 or 12, wherein the vacuum system comprises a vacuum pump and at least one conduit between the vacuum pump and the vacuum chamber for evacuating gas therethrough, wherein the control circuitry is configured to control the vacuum system so as to evacuate the vacuum chamber through a conduit having a gas passage therethrough that is relatively restricted in the second mode, and to evacuate the vacuum chamber through a conduit having a gas passage therethrough that is less restricted in the first mode.

14. The spectrometer of claim 10, 11 or 12, comprising:a) a first conduit between the vacuum pump and the vacuum chamber that comprises a first valve, and a second, different conduit between the vacuum pump and the vacuum chamber that comprises a second valve; wherein the control circuitry is configured such that in the first mode the spectrometer opens the first valve whilst maintaining the second valve closed such that the vacuum pump evacuates the vacuum chamber through the first conduit, and in the second mode opens the second valve whilst maintaining the first valve closed such that the vacuum pump evacuates the vacuum chamber through the second conduit; wherein the second conduit provides a gas passage therethrough, when the second valve is open, that is relatively restricted and the first conduit provides a gas passage therethrough, when the first valve is open, that is less restricted; orb) a first conduit between the vacuum pump and the vacuum chamber that comprises a first valve, and a second, different conduit between the vacuum pump and the vacuum chamber that comprises a second valve; wherein the control circuitry is configured such that in the second mode the spectrometer opens the first valve whilst maintaining the second valve closed such that the vacuum pump evacuates the vacuum chamber through the first conduit, and in the first mode opens both the first and second valves such that the vacuum pump evacuates the vacuum chamber through both the first and second conduits.

15. The spectrometer of any preceding claim, comprising a further vacuum chamber downstream of said vacuum chamber, and a turbomolecular pump connected to the further vacuum chamber for evacuating the further vacuumchamber, wherein a gas inlet to said vacuum pump is connected to a gas exhaust from said turbomolecular pump.

16. A mass spectrometer comprising:a vacuum chamber;a first orifice in an upstream wall of the vacuum chamber for allowing ions therethrough; anda second, smaller orifice in the upstream wall of the vacuum chamber for allowing ions therethrough;wherein either:a) the mass spectrometer is configured to be operable in a first mode in which ions are transmitted through the first orifice but not the second orifice, and in a second mode in which ions are transmitted through the second orifice but not the first orifice; orb) the mass spectrometer is configured to transmit ions simultaneously through both the first and second orifices, and wherein the mass spectrometer is configured to be operable in a first mode in which ions that have passed through the first orifice, or ions derived therefrom, are transmitted to a mass analyser in the spectrometer, whereas ions that have passed through the second orifice are filtered out; and wherein the mass spectrometer is configured to be operable in a second mode in which ions that have passed through the second orifice, or ions derived therefrom, are transmitted to the mass analyser, whereas ions that have passed through the first orifice are filtered out.

17. A mass spectrometer comprising:a vacuum chamber;a first orifice in an upstream wall of the vacuum chamber for allowing ions therethrough; anda second orifice in the upstream wall of the vacuum chamber for allowing ions therethrough;wherein either:a) the mass spectrometer is configured to be operable in a first mode in which ions are simultaneously transmitted through both the first orifice and the second orifice, and in a second mode in which ions are transmitted through the first orifice but not the second orifice; orb) the mass spectrometer is configured to transmit ions simultaneously through both the first and second orifices, and wherein the mass spectrometer is configured to operable in: a first mode in which ions that have passed through both the first orifice and the second orifice, or ions derived therefrom, are transmitted to a mass analyser in the spectrometer; and in a second mode in which ions that have passed through the first orifice, or ions derived therefrom, are transmitted to the mass analyser, whereas ions that are that have passed through the second orifice are filtered out.

18. A mass spectrometry system comprising:a mass spectrometer configured to be operable in a first, relatively high sensitivity mode and in a second, lower sensitivity mode;an input device for receiving an indication of a type of assay that a sample is to be analysed by; andcontrol circuitry configured to control the mass spectrometer to automatically operate in the first mode or the second mode based on said indication of the type of assay that the sample is to be analysed by.

19. A mass spectrometry system comprising:a mass spectrometer as claimed in any preceding claim;a sample reader for reading identifiers on samples received at the system; andcontrol circuitry configured to control the system to:i) automatically determine the type of assay that each of the samples is required to be analysed by from information in the identifiers read by the sample reader;ii) automatically determine which of the first and second modes the mass spectrometer is to be operated in when analysing a given one of the samples based on the type of assay that it has been determined as being required to be analysed by; andiii) in response to step ii), control the mass spectrometer to mass analyse said sample whilst operating in the determined mode.

20. A method of mass spectrometry comprising:providing a mass spectrometer as claimed in any preceding claim;operating the mass spectrometer in the first mode whilst mass analysing ions; andoperating the mass spectrometer in the second mode whilst mass analysing ions.

521. A method of mass spectrometry comprising:transmitting ions through an orifice into a vacuum chamber and towards a mass analyser in both a first mode and a second mode, wherein the orifice has a relatively large area in the first mode and a relatively small area in the second10 mode.

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