Automated beam check

Abstract

A method of automatically performing a routine to check the operational state of a mass spectrometer is disclosed wherein the method is performed automatically as a start-up routine upon switching ON the mass spectrometer. The method comprises automatically generating a vacuum within one or more vacuum chambers of a mass spectrometer and automatically generating first ions using an internal ion source, wherein the internal ion source is located within a vacuum chamber of the mass spectrometer or is located within a chamber downstream from an atmospheric pressure interface, and detecting at least some of the first ions or second ions derived from the first ions. The method further comprises automatically determining whether or not the mass spectrometer is in a correct operational state.

Claims

1. A method of automatically performing a routine to check the operational state of a mass spectrometer, said method comprising: (i) automatically generating a vacuum within one or more vacuum chambers of a mass spectrometer; (ii) automatically generating first ions using an internal ion source, wherein said internal ion source is located within a vacuum chamber of said mass spectrometer or is located within a chamber downstream from an atmospheric pressure interface, and detecting at least some of said first ions or second ions derived from said first ions; and then (iii) automatically determining whether or not said mass spectrometer is in a correct operational state, wherein said method is performed automatically as a start-up routine upon switching ON said mass spectrometer.

2. A method as claimed in claim 1, wherein said ion source comprises an Electron Impact (“EI”) ion source or a Glow Discharge (“GD”) ion source.

3. A method as claimed in claim 1, wherein the step of determining whether or not said mass spectrometer is in a correct operational state comprises determining whether or not said first ions and/or said second ions are detected by an ion detector.

4. A method as claimed in claim 1, wherein the step of determining whether or not said mass spectrometer is in a correct operational state comprises determining whether or not first ions having mass to charge ratios within one or more defined ranges and/or second ions having mass to charge ratios within one or more defined ranges are detected by an ion detector.

5. A method as claimed in claim 1, wherein the step of determining whether or not said mass spectrometer is in a correct operational state comprises determining whether or not the mass resolution of said first ions and/or the mass resolution of said second ions is within a desired range.

6. A method as claimed in claim 1, wherein the step of determining whether or not said mass spectrometer is in a correct operational state comprises determining whether or not the determined mass, mass to charge ratio or mass position of said first ions and/or said second ions is within a desired range.

7. A method as claimed in claim 1, further comprising entering an error state if it is determined that said mass spectrometer is not in a correct operational state.

8. A method as claimed in claim 1, further comprising automatically retuning and/or automatically recalibrating said mass spectrometer if it is determined that said mass spectrometer is not in a correct operational state.

9. A method as claimed in claim 1, further comprising automatically repeating one or more test or other procedures if it determined that said mass spectrometer is not in a correct operational state.

10. A method as claimed in claim 1, further comprising automatically adjusting, resetting or resending one or more control parameters, voltages or signals if it determined that said mass spectrometer is not in a correct operational state.

11. A mass spectrometer comprising: an internal ion source located within a vacuum chamber of said mass spectrometer or located within a chamber downstream from an atmospheric pressure interface; and a control system which is arranged and adapted to perform a routine to check the operational state of the mass spectrometer automatically as a start-up routine upon switching ON said mass spectrometer, wherein said control system is arranged and adapted: (i) automatically to generate a vacuum within one or more vacuum chambers of the mass spectrometer; (ii) automatically to generate first ions using said internal ion source and to detect at least some of said first ions or second ions derived from said first ions; and then (iii) automatically to determine whether or not said mass spectrometer is in a correct operational state.

12. A method of automatically performing a routine to check the operational state of a mass spectrometer, the method comprising: (i) automatically generating first ions using an internal ion source, wherein the internal ion source is located within a vacuum chamber of the mass spectrometer or is located within a chamber downstream from an atmospheric pressure interface, and detecting at least some of the first ions or second ions derived from the first ions; and then (ii) automatically determining whether or not the mass spectrometer is in a correct operational state, wherein the method is performed automatically at a predetermined service interval.

13. A method as claimed in claim 12, wherein the predetermined service interval is upon start-up or switching ON the mass spectrometer.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

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

(2) FIG. 1 shows an atmospheric pressure interface of a miniature mass spectrometer according to a preferred embodiment of the present invention wherein an internal ion source for automatically generating calibration ions is provided in addition to a conventional external ion source for generating analyte ions;

(3) FIG. 2 shows a miniature mass spectrometer according to a preferred embodiment of the present invention;

(4) FIG. 3A shows a mass spectrum of a preferred calibration compound which was obtained in a positive ion mode indicating how a wide range of mass spectral peaks may be observed across a wide mass range and FIG. 3B shows a corresponding mass spectrum of the same calibration compound obtained in negative ion mode and which shows an improved and more consistent spread of mass spectral peaks; and

(5) FIG. 4 shows a flow diagram of a preferred start-up routine according to an embodiment of the present invention and which indicates the automatic checks and test which are preferably made before the control system of the mass spectrometer places the mass spectrometer either in a pass or fail state.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

(6) The preferred embodiment relates to a mass spectrometer based chromatography detector for a High Pressure Liquid Chromatography (“HPLC”) or similar system which utilises an automated method to measure directly the working state of the instrument or mass spectrometer.

(7) The automated method preferably comprises an automated start-up routine which is preferably performed upon switching ON the mass spectrometer. The start-up routine is particularly useful for ensuring that a miniature mass spectrometer is in a correct operational state before being used by a user who may have no prior experience of operating a mass spectrometer.

(8) A preferred miniature mass spectrometer will first be described with reference to FIGS. 1-2.

(9) According to a particularly preferred embodiment the preferred automatic start-up routine is preferably implemented on a miniature mass spectrometer as shown in FIG. 1 which has an internal glow discharge ion source 1 as a secondary source of ions.

(10) The preferred miniature mass spectrometer preferably comprises an Electrospray Ionisation (“ESI”) ion source 2 which generates analyte ions which are preferably introduced into an ion block 4 of the mass spectrometer via a sample cone 3 which is attached to the ion block 4. The ion block 4 is preferably secured to the main housing of the mass spectrometer. The main housing of the mass spectrometer preferably incorporates multiple vacuum chambers (not shown).

(11) Gas and/or a liquid may be held in a reservoir 5 and vapour is preferably passed via a solenoid valve 6 to a smaller chamber located within the body of the ion block 4. A sharp needle 7 is preferably provided within the chamber. A glow discharge is preferably formed within the chamber by applying a high voltage to the needle 7 with the result that vapour which is directed towards the needle 7 is preferably ionised to generate calibration or other ions. The calibration or other ions are then preferably emitted into the main internal passage within the ion block 4 such that the calibration or other ions are then preferably passed into the main housing of the mass spectrometer.

(12) The sharp needle 7 is preferably placed in a small volume within the ion block 4 at a pressure of approximately 4 mbar. A small orifice preferably leads from the glow discharge region into the main ion block 4. A high voltage DC potential of approximately 800 V is preferably applied to the sharp needle 7 in order to initiate a glow discharge. Vaporized calibrant is preferably provided to the ion source by heating a small reservoir 5 which is partially filled with a liquid calibrant. A solenoid valve 6 is then preferably opened between the glow discharge source (at vacuum) and the reservoir 5. The reservoir 5 is preferably nominally at atmospheric pressure and a known length of capillary into the reservoir 5 from an ambient environment (atmosphere or a nitrogen gas line) preferably provides a fixed controlled leak which aids in the transport of vapour to the ion source.

(13) A particularly preferred compound for calibration purposes is Fomblin Y which is a perfluoropolyether compound and which has been used as a vacuum pump oil due to its inertness, stability and low vapour pressure.

(14) FIG. 2 shows an overall representation of a miniature mass spectrometer according to a preferred embodiment of the present invention. An Electrospray ion source 2 preferably generates analyte ions which pass via a sample cone 3 into a main internal passage within the ion block 4. An internal glow discharge ion source 8 is located within the body of the ion block 4 and is preferably arranged to generate calibration or other ions. The resulting calibration or other ions are preferably emitted directly into the main internal passage within the ion block 4.

(15) Analyte ions generated by the external ion source 2 and calibration or other ions generated by the internal ion source 8 are preferably directed into a first vacuum chamber 9 located within the main housing of the mass spectrometer. The first vacuum chamber 9 preferably houses a stepwave ion guide 12 i.e. a conjoined ion guide assembly wherein ions are preferably transferred in a generally radial direction from a first ion path formed within a first plurality of ring electrodes into a second ion path formed by a second plurality of ring electrodes. The first and second plurality of ring electrodes are preferably conjoined along at least a portion of their length. Ions are preferably radially confined within the first and second plurality of ring electrodes.

(16) The second ion path is preferably aligned with a differential pumping aperture which preferably leads into a second vacuum chamber 10 housing a second ion guide 13. The second ion guide 13 preferably comprises an ion tunnel ion guide comprising a plurality of ring electrodes each having an aperture. Ions preferably pass through the apertures in each of the ring electrodes.

(17) The ions are then preferably passed through a further differential pumping aperture into a third vacuum chamber 11 which preferably houses a quadrupole mass filter 14 and an ion detector 15. Other embodiments are contemplated wherein a different arrangement of ion guides may be provided and a mass analyser other than a quadrupole rod set mass analyser may be provided.

(18) Automatic Routine

(19) An automatic routine which is preferably performed by the mass spectrometer will now be described in more detail.

(20) The determination of the working state (or otherwise) of the mass spectrometer is preferably automated such that once the mass spectrometer is powered ON by the user or operator, the mass spectrometer then preferably automatically pumps itself down. Once the mass spectrometer has automatically pumped itself down the control system then preferably automatically turns ON one or more high voltage (“HV”) power supplies and/or may also turn ON one or more gas supplies when a sufficient vacuum level is reached.

(21) The mass spectrometer then preferably acquires mass spectral data in order to determine that the mass spectrometer is working within predefined parameters and is preferably in a correct operational state.

(22) According to a preferred embodiment an integrated or internal source of calibration or other ions is preferably utilised. The operation of the internal calibration source preferably does not require any input from a user. Calibration or other ions are preferably automatically generated and are preferably automatically directed into the mass analyser. The calibration or other ions are preferably subsequently detected and mass analysed as part of the automatic start-up routine according to a preferred embodiment of the present invention.

(23) The source of calibration or other ions is preferably generated using an ion source of the mass spectrometer.

(24) According to an embodiment an intrinsic source of ions may be used. For example, atmospheric gas molecules (e.g. oxygen, nitrogen) and/or water or solvent molecules which preferably continuously elute from a liquid chromatography (“LC”) system even when a separation is not taking place may be used.

(25) A secondary source of molecules may alternatively be provided and may either be directed into the liquid flow into the ion source or else may be introduced into one of the gas flows into the ion source.

(26) According to an embodiment a secondary ion source may be provided in order to generate calibration or other ions. The secondary ion source may comprise an additional external ion source such as an (additional) Electrospray Ionisation (“ESI”) ion source or an Atmospheric Pressure Chemical Ionisation (“APCI”) ion source.

(27) Accordingly to the preferred embodiment the secondary ion source is located internal to or within the vacuum system of the mass spectrometer. For example, according to the preferred embodiment the internal ion source may comprise an Electron Impact (“EI”) ionisation or a Glow Discharge (“GD”) ion source. The secondary ion source may be arranged to generate ions from intrinsic molecules such as atmospheric oxygen or nitrogen or alternatively and more preferably from an additional source such as a vial containing a calibration compound.

(28) There are various methodologies and parameters that may be measured to determine whether or not the mass spectrometer is in a correct operational state. Some of the various determinations which may be made by the preferred control system are described in more detail below.

(29) 1. Determining whether or not an Ion Beam is Present

(30) According to an embodiment a simple determination may be made as to whether or not an ion beam is present. According to this embodiment a non-resolved ion beam (i.e. an ion beam which is not mass filtered) may be generated and the existence or otherwise of an ion current above a defined threshold may be used to determine that the mass spectrometer is working at least at a basic level.

(31) 2. Determining whether or not a Resolved ion Beam is Detected

(32) According to an embodiment a determination may be made as to whether or not a mass or mass to charge ratio resolved ion beam is detected.

(33) This determination may be made independently of whether or not a prior determination has been made that an ion beam is present as detailed above.

(34) According to this embodiment a quadrupole mass filter is preferably set to resolve (i.e. mass filter or mass select) an ion beam so that an ion beam is onwardly transmitted which has a known or defined range of mass to charge ratios.

(35) According to this embodiment the mass spectrometer preferably determines whether or not ions having mass to charge ratios within the mass to charge ratio transmission window transmitted by the mass filter are detected by an ion detector.

(36) 3. Determining whether or not Multiple Resolved ions are Detected

(37) According to an embodiment a determination may be made as to whether or not multiple mass or mass to charge ratio resolved ions are detected.

(38) This determination may be made independently of whether or not a prior determination has been made as detailed above.

(39) According to this embodiment a quadrupole mass filter or other mass filtering device is preferably set or otherwise arranged to transmit ions having mass to charge ratios within certain mass windows and a resulting mass spectrum may be generated.

(40) 4. Determining Whether or not Ions have been Resolved Correctly

(41) According to an embodiment a determination may be made as to whether or not ions have been mass or mass to charge ratio resolved correctly.

(42) This determination may be made independently of whether or not a prior determination has been made as detailed above.

(43) According to this embodiment the mass resolution of one or more ions may be measured in addition to intensity.

(44) 5. Determining Whether or not Mass has been Measured Correctly

(45) According to an embodiment a determination may be made as to whether or not the mass of ions has been measured correctly.

(46) This determination may be made independently of whether or not a prior determination has been made as detailed above.

(47) According to this embodiment the mass position of one or more ions is preferably measured in addition to intensity and/or resolution.

(48) 6. Determining Whether or not to Auto-Retune

(49) According to an embodiment a determination may be made as to whether or not to auto-retune.

(50) This determination may be made independently of whether or not a prior determination has been made as detailed above.

(51) According to this embodiment in the circumstance that one of the determinations as detailed above such as either the intensity, the resolution or the mass position not meeting a given requirement, then the mass spectrometer is preferably arranged to perform an automated procedure to re-set its resolution and/or to re-calibrate its mass position.

(52) A determination to automatically retune the mass spectrometer may also be made upon criteria other than the criteria discussed above.

(53) Further Details

(54) Various automatic start-up procedures were performed using a miniature mass spectrometer substantially as shown in FIGS. 1 and 2.

(55) According to an embodiment a first mass spectrum of preferred calibration ions generated from Fomblin Y was obtained in positive ion mode and is shown in FIG. 3A and a second mass spectrum of preferred calibration ions generated from Fomblin Y was obtained in negative ion mode and is shown in FIG. 3B.

(56) The mass spectra, particularly the mass spectrum shown in FIG. 3B which was obtained in negative ion mode, show an evenly spaced series of ions distributed across the mass range with a relatively low variation in intensity. Both these traits are highly desirable in a calibration compound.

(57) Furthermore, since the preferred calibration compound (Fomblin Y) has a low vapour pressure and has widespread use as a vacuum oil, any inadvertent contamination of the mass spectrometer is preferably avoided.

(58) An example of an automated start-up routine that may be pursued by a control system of a mass spectrometer according to an embodiment of the present invention is shown in FIG. 4 and will be described in more detail below.

(59) According to a preferred embodiment upon switching the mass spectrometer ON as an initial step 16, the mass spectrometer is preferably arranged to automatically start pumping 17 the various vacuum chambers. A determination 18 is then preferably made that the vacuum pressures are within correct operational ranges. The mass spectrometer then preferably proceeds to switching into an operational mode 19 and subsequent determinations are preferably automatically made that the mass spectrometer is in a correct operational state.

(60) According to a less preferred embodiment of the present invention a user may initiate 20 the mass spectrometer to perform a routine to check the operational state of the mass spectrometer. The user may initiate the routine after it has been established that the vacuum pressures are in a correct operational range. It is not essential, therefore, that the routine is performed upon start-up, although performing the routine automatically upon start-up is particularly preferred. Other embodiments are also contemplated wherein a check may be made as to the operational state of the mass spectrometer at a predetermined service interval (e.g. after a predetermined number of operational hours, after a predetermined period of time or after a predetermined number of experimental acquisitions have been performed etc.)

(61) The routine to check the operational state of the mass spectrometer preferably comprises switching an ion source ON 21. The ion source preferably comprises an internal ion source such as a glow discharge ion source as shown and described above with reference to FIGS. 1 and 2. Data is preferably acquired 22 and a determination is then preferably made at a subsequent step 23 as to whether or not an intensity threshold has been met. If the intensity threshold is met then the routine preferably proceeds to a step 24 wherein it is determined whether or not to check the resolution of the ion beam. If the intensity threshold is not met then the routine preferably proceeds to a fail step 25 wherein the mass spectrometer is considered not to be in a correct operational state.

(62) If it is not desired to check the resolution of the ion beam then the routine may then proceed directly to a pass step 26 wherein the mass spectrometer is considered to be in a correct operational step.

(63) If it is desired to check the resolution then the routine then preferably proceeds to a step 27 wherein a determination is made as to whether or not the resolution is met. If the resolution is not met then the routine preferably proceeds to a fail step 25 as detailed above. If the resolution is met then the routine preferably proceeds to a further step 28 wherein a check is preferably made as to whether or not it is desired to check the mass position. If it is not desired to check the mass position then the routine then preferably proceeds to the pass step 26 as detailed above. If it is desired to check the mass position then the routine preferably proceeds to a step 29 wherein a determination is made as to whether or not the mass position requirement(s) are met.

(64) If the mass position requirement(s) are met then the routine preferably passes to the pass stage 26 as detailed above. If the mass position requirement(s) are not met then the routine preferably passes to the fail stage 25 as detailed above.

(65) Various alternative embodiments are contemplated. In particular, determinations as to whether or not an intensity threshold is met 23, as to whether or not a resolution is met 27 and as to whether or not mass position requirement(s) are met 29 may be performed in a different order to the order illustrated by the flow diagram shown in FIG. 4.

(66) Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.