Charge detection for ION current control

Abstract

A method for controlling the filling of an ion trap with a predetermined quantity of ions. The method comprises generating an ion current by transmitting ions along an ion path to an ion trap, such that ions are accumulated in the ion trap over a transmission time period, wherein the magnitude of the ion current varies in time. The method further comprises detecting at an ion detector at least some ions from the source of ions during a plurality of distinct sampling time intervals interspersed within the transmission time period, and setting the duration of the transmission time period based on the detection of ions at the ion detector. The time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than a timescale for variation of the magnitude of the ion current. A controller for controlling the filling of an ion trap with a predetermined quantity of ions and a mass spectrometer comprising the controller is also described.

Claims

1. A method for controlling the filling of an ion trap with a predetermined quantity of ions, the method comprising: generating an ion current by transmitting ions along an ion path, the ion path extending from a source of ions to an ion trap such that ions are accumulated in the ion trap over a transmission time period, wherein the magnitude of the ion current varies in time; detecting at an ion detector at least some ions from the source of ions during a plurality of distinct sampling time intervals interspersed within the transmission time period; setting the duration of the transmission time period based on the detection of ions at the ion detector; and wherein the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than a timescale for variation of the magnitude of the ion current, the timescale for variation being a period of time that the ion current undergoes a threshold change in its magnitude.

2. The method of claim 1, wherein setting the duration of the transmission time period based on the detection of ions at the ion detector comprises setting the transmission time period based on the total quantity of ions detected at the ion detector during the plurality of sampling time intervals.

3. The method of claim 1, wherein the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than a predefined percentage of the timescale for variation of the magnitude of the ion current.

4. The method of claim 3, wherein the predefined percentage is one of: 10%, 20%, 50%, or 90%.

5. The method of claim 1, wherein the timescale for variation of the magnitude of the ion current is an average period of the current variation.

6. The method of claim 1, wherein the timescale for variation of the magnitude of the ion current is determined based on a transform of the ion current to the frequency domain.

7. The method of claim 1, wherein the timescale for variation of the magnitude of the ion current is the average time period in which the ion current changes by at least a predetermined percentage of its maximum magnitude.

8. The method of claim 1, wherein the timescale for variation of the magnitude of the ion current is the average time difference between instances of the ion current being equal to the moving average magnitude of the ion current.

9. The method of claim 1, wherein the magnitude of the ion current varies approximately stepwise, and the timescale for variation of the magnitude of the ion current is the average width of peaks in the derivative of the ion current against time.

10. The method of claim 1, wherein the method further comprises, prior to detecting at the ion detector at least some ions from the source of ions during a plurality of distinct sampling time intervals, steps of: receiving a measurement of the ion current over a pre-measurement time period; and determining the timescale for variation of the magnitude of the ion current over the premeasurement time period.

11. The method of claim 1, further comprising: providing at least one ion detector along the ion path, between the source of ions and the ion trap.

12. The method of claim 1, wherein detecting at an ion detector at least some ions from the source of ions during a plurality of distinct sampling time intervals comprises, prior to detecting the at least some ions, directing the at least some ions from the ion path towards the ion detector during each distinct sampling time interval.

13. The method of claim 12, further comprising: providing the one ion detector external to the ion path; providing at least one switching device along the ion path, arranged between the source of ions and the ion trap; wherein the switching device is configured to direct ions from the source of ions towards the ion detector external to the ion path during each distinct sampling time interval.

14. The method of claim 1, further comprising: terminating the transmission of ions along the ion path once the transmission period has elapsed.

15. The method of claim 1, wherein setting the duration of the transmission time period comprises terminating the transmission of ions along the ion path when a total quantity of ions detected at the ion detector during the plurality of sampling time intervals exceeds a pre-defined value.

16. The method of claim 1, further comprising: providing at least one gas-filled ion guide along the ion path, between the source of ions and the ion trap.

17. The method of claim 16, wherein the timescale for variation of the magnitude of the ion current is less than a temporal broadening of step changes in the magnitude of an ion current entering the gas-filled ion trap, resulting from ion collisions with gas in the gas-filled guide.

18. A controller for controlling the filling of an ion trap with a predetermined quantity of ions, the controller configured to: receive a measurement based on a quantity of ions detected at an ion detector during a plurality of distinct sampling time intervals, the ions transmitted from a source of ions, wherein an ion path extends from the source of ions to an ion trap such that ions are accumulated at the ion trap over a transmission time period, wherein ions transmitted along the ion path generate an ion current and the magnitude of the ion current varies in time, and wherein the plurality of distinct sampling time intervals interspersed within the transmission time period; and set the duration of the transmission time period based on the ions detected at the ion detector; and wherein the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than the timescale for variation of the magnitude of the ion current, the timescale for variation being a period of time that the ion current undergoes a threshold change in its magnitude.

19. The controller of claim 18, wherein the controller is configured to set the duration of the transmission time period based on the total quantity of ions detected at the ion detector during the plurality of sampling time intervals.

20. The controller of claim 18, wherein the controller is further configured to: set the duration of the sampling time interval.

21. The controller of claim 18, further configured to: set the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval.

22. The controller of claim 21, further configured to: set the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval to be less than a predefined percentage of the timescale for variation of the magnitude of the ion current.

23. The controller of claim 22, wherein the predefined percentage is one of: 10%, 20%, 50%, or 90%.

24. The controller of claim 18, wherein the timescale for variation of the magnitude of the ion current is the average period of the current variation.

25. The controller of claim 18, wherein the timescale for variation of the magnitude of the ion current is determined based on a transform of the ion current to the frequency domain.

26. The controller of claim 18, wherein the timescale for variation of the magnitude of the ion current is the average time period in which the ion current changes by at least a predetermined percentage of its maximum magnitude.

27. The controller of claim 18, wherein the timescale for variation of the magnitude of the ion current is the average time difference between instances of the ion current being equal to the moving average magnitude of the ion current.

28. The controller of claim 18, wherein the magnitude of the ion current varies approximately stepwise, and the timescale for variation of the magnitude of the ion current is the average width of peaks in the derivative of the ion current against time.

29. The controller of claim 18, wherein prior to receiving the measurement based on a quantity of ions detected at an ion detector during the plurality of distinct sampling time intervals, the controller is further configured to: receive a measurement of the ion current during a pre-measurement time period; and determine the timescale for variation of the magnitude of the ion current during the pre-measurement time period.

30. The controller of claim 18, wherein the ion detector is arranged external to the ion path, the controller further configured to: control a switching device arranged along the ion path between the source of ions and the ion trap, the switching device configured to direct ions from the source of ions to the ion detector; wherein the controller is configured to control the switching device to direct ions from the source of ions towards the ion detector external to the ion path during each distinct sampling time interval.

31. The controller of claim 18, further configured to: terminate the transmission of ions along the ion path once the transmission period has elapsed.

32. The controller of claim 18, wherein the controller configured to set the duration of the transmission time period based on the total quantity of ions detected at the ion detector during the sampling time intervals comprises the controller configured to terminate the transmission of ions along an ion path when the measurement of the total quantity of ions detected at the ion detector exceeds a pre-defined value.

33. A mass spectrometer comprising: a source of ions; an ion trap, arranged to receive ions transmitted along an ion path extending from the source of ions to the ion trap; an ion detector arranged to be capable of detecting at least some ions from the source of ions; a mass analyser, arranged to receive at least some ions from the ion trap; and a controller configured to: receive a measurement based on a quantity of ions detected at the ion detector during a plurality of distinct sampling time intervals, the ions transmitted from the source of ions, wherein an ion path extends from the source of ions to the ion trap such that ions are accumulated at the ion trap over a transmission time period, wherein ions transmitted along the ion path generate an ion current and the magnitude of the ion current varies in time, and wherein the plurality of distinct sampling time intervals interspersed within the transmission time period, set the duration of the transmission time period based on the ions detected at the ion detector, wherein the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than the timescale for variation of the magnitude of the ion current, the timescale for variation being a period of time that the ion current undergoes a threshold change in its magnitude.

34. The mass spectrometer of claim 33, wherein the ion detector is external to the ion path, the mass spectrometer further comprising: an ion gate arranged along the ion path between the source of ions and the ion trap, the ion gate capable of directing ions from the source of ions towards the ion detector external to the ion path.

Description

LIST OF FIGURES

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

(2) FIG. 1 is a schematic representation of an apparatus implementing a method for controlling the filling of an ion trap with a predetermined quantity of ions.

(3) FIG. 2 is a schematic representation of an apparatus implementing a method for controlling the filling of an ion trap with a predetermined quantity of ions, according to a second example.

(4) FIG. 3 is a flow diagram illustrating a method for controlling the filling of an ion trap with a predetermined quantity of ions;

(5) FIG. 4 is a flow diagram illustrating a method for controlling the filling of an ion trap with a predetermined quantity of ions, according to a second example;

(6) FIG. 5A is a schematic representation of an ion current which varies in time, and a first measure of a timescale of variation of the ion current;

(7) FIG. 5B is a schematic representation of an ion current which varies in time, and a second measure of a timescale of variation of the ion current;

(8) FIG. 5C is a schematic representation of an ion current which varies in time, and a third measure of a timescale of variation of the ion current;

(9) FIG. 5D and FIG. 5E is a schematic representation of an ion current which varies in time, and a fourth measure of a timescale of variation of the ion current;

(10) FIG. 5F and FIG. 5G is a schematic representation of an ion current which varies in time, and a fifth measure of a timescale of variation of the ion current;

(11) FIG. 6 is a schematic representation of an apparatus implementing a method for controlling the filling of an ion trap with a predetermined quantity of ions, according to a third example;

(12) FIG. 7 is a schematic representation of an apparatus implementing a method for controlling the filling of an ion trap with a predetermined quantity of ions, according to a fourth example;

(13) FIG. 8 is a plot illustrating the voltages applied to ion optics during operation of the example of FIG. 6;

(14) FIG. 9 illustrates electrical circuitry employed together with the described examples;

(15) FIG. 10 is a schematic representation of an orbital-trapping mass spectrometer arranged to implement a method for controlling the filling of an ion trap with a predetermined quantity of ions; and

(16) FIG. 11 is a plot of the signal-to-noise ratio of ions measured in a mass spectrometer of the type shown in FIG. 10.

(17) In the drawings, like parts are denoted by like reference numerals. The drawings are not drawn to scale.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

(18) FIG. 1 shows schematically a portion of a mass spectrometer for performing the method of the invention. FIG. 1 also shows a controller which is an embodiment of the invention.

(19) Specifically, FIG. 1 includes a source of ions 10. In this case, the source of ions is an electrospray or plasma ion source operating at atmospheric pressure and followed by atmosphere-to-vacuum interface and at least one RF ion guide, although other types of sources of ions such as an ion source or devices for storing ions could be used (such as an electron impact (EI) source or MALDI source at low or high pressure). FIG. 1 further includes an ion trap 14. In this example, the ion trap is a linear trap, although the described method is not limited to this type of ion trap. An ion path 18 extends between the source of ions 10 and the ion trap 14. Ions from the ion source 10 can pass along the ion path 18 and be received at the ion trap 14. Ions received at the ion trap 14 are at least temporarily stored or trapped therein. It will be appreciated that in the whole mass spectrometer, there may be one or more other ion optical devices provided, for example between the ion source 10 and the ion trap 14, such as ion guides, mass filters etc. as known in the art. The ion trap 14 may be a mass analysing ion trap or a mass analyser may be provided downstream of the ion trap 14 to receive ions from the ion trap.

(20) An ion detector 12 is arranged on the ion path 18, between the source of ions 10 and the ion trap 14. The detector 12 can be used to detect (or ‘sample’) at least a portion of the ions transmitted along the ion path 18. Specifically, the detector 12 is used to detect at least some ions transmitted from the source of ions 10 during a plurality of distinct sampling time intervals. The detector 12 may be an image current detector, and thus does not collect or receive the sampled portion of ions. Alternatively, the detector 12 may be another type of ion detector, which requires collection of the sampled portion of ions in order for detection to take place. During a period of transmission of ions from the source of ions 10 (the “transmission time period”), the ions may either traverse through the detector 12 to reach the ion trap 14, or (in some cases, dependent on the type of detector) may instead be collected and detected at the detector 12.

(21) A controller 16 is arranged to be in communication with the detector 12, and receive measurements therefrom. The controller 16 is configured to control the operation of the source of ions 10 and the ion trap 14 (either directly, or through additional ion optics not shown in FIG. 1).

(22) As noted above, it is highly desirable to precisely control the filling of the ion trap. That is to say, it is desirable to control the quantity of ions stored within the ion trap at the end of a period of transmission of ions from the source of ions 10 and along the ion path 18 (the “transmission time period”). To accomplish control of the filling of the trap, the present invention ‘samples’ at the detector at least a portion of ions transmitted from the source of ions 10 along the ion path. The detector samples the ions during a plurality of distinct sampling time intervals interspersed within the transmission time period.

(23) For instance, in the embodiment of FIG. 1, ions may be transmitted from the source of ions 10 and towards the ion trap 14 for a transmission time period. For the majority of this transmission time period, ions traverse the ion path 18 and are received at the ion trap 14. However, for at least two relatively short time intervals (“sampling time intervals”) within the transmission time period, the detector 12 detects at least some ions transmitted from the ion source. In other words, the detector 12 intercepts ions traversing the ion path 18 during the sampling time intervals. Detection or ‘sampling’ of the ion current takes place only during the plurality of sampling time intervals.

(24) The sampling time intervals are each much shorter than the transmission time period. In the specific example of FIG. 1, the transmission time period is 100 ms, whereas the sampling time intervals are each 10 μs. The sampling time intervals are interspersed throughout the transmission time period. In the example of FIG. 1, the sampling time intervals are interspersed equally. In other words, the time between each sampling time interval is equal. The time between each sampling time interval is sometimes denoted as an “accumulation interval” in the present specification, and can represent the time periods during which ions are accumulating at the ion trap 14. However, it should be noted that in some examples, only a portion of the ions traversing the ion path 18 during a sampling time interval are received at the detector 12. In this scenario, accumulation of ions may take place at the trap during both the sampling time intervals and the accumulation intervals. As such, accumulation of ions takes place at the trap 14 over the transmission time period as a whole.

(25) In the present example, the accumulation intervals are 90 μs. Around 1000 sampling time intervals are interspersed during the transmission time period, having an accumulation time interval in between. As such, only a small proportion of the ions transmitted from the source of ions 10 are received at the detector 12, with the majority of the ions transmitted from the source of ions 10 being received at the ion trap 14. In the present example, the percentage of ions transmitted from the source of ions 10 and received at the ion detector 12 would be around 10%. However, the ion current sampled at the detector 12 provides an indication of any variation of the ion current during the transmission time period.

(26) In practice, even a source of ions supplying a nominally constant ion current will demonstrate a variation in the magnitude of the ion current over time. The specific nature of the variation of the ion current will depend on a number of factors including the type of ion source, for instance. Nevertheless, the magnitude of the ion current varies in time over a particular timescale. The timescale can in some cases be considered a characteristic time for the variation, or an approximate period for the variation. As such, in the described method the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval (related to the frequency of the sampling time intervals within the transmission time period) is set to be less than the timescale for variation of the magnitude of the ion current. Setting the time difference in this way has the particular advantage that the frequency of sampling at the detector 12 is sufficiently fast to capture or detect the variation in the magnitude of the ion current.

(27) Capturing the variation of the magnitude of the ion current by appropriately setting the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval to be less than the timescale of variation of the ion current, allows the present invention to more accurately monitor and predict the rate of filling at the ion trap 14. In particular, periods during which the filling rate at the ion trap 14 is increased (as a result of a higher ion current) can be taken into account. As such, the transmission time period over which a predetermined quantity of ions will be received at the ion trap 14 can be more accurately predicted.

(28) Accordingly, the transmission time can be estimated and subsequently set as ions are detected at the detector 12 during the plurality of sampling time intervals. The transmission time period can be estimated by extrapolation of the measured rate of ions received at the detector 12, for instance. Alternative algorithms for defining the proportionality between the number of ions (or the ion current) detected at the detector 12 can be envisaged.

(29) Thus, the estimation (or calculation) of the transmission time period is a dynamic process throughout the transmission time period. In the present example, a new estimation of the transmission time period is calculated at the end of each sampling time interval, based on the total ions received at the detector 12 during any preceding sampling time interval. The process of detection of ions at the detector 12 during each sampling time interval accordingly provides feedback to the system, in order to estimate and set the transmission time period in an iterative way.

(30) In the present example, the ion detector 12 could include a grid in the way of ions on the ion path 18, in order to advantageously enable direct and uninterrupted detection of ions or secondary particles. In this case, the time difference between the start of each sampling time interval can be made very short if desired, being defined just by the acquisition rate of the detection electronics. Where ions are detected, an electrometer could be used, while in the case of detection of secondary particles either an electrometer or electron multiplier could be employed. Nevertheless, to avoid contamination and charging up from ion beams, the grid should be heated or periodically flushed with ozone or oxygen plasma.

(31) In summary, the present inventors have recognised prior art methods of estimation of a filling time of the ion trap are inadequate when an ion current is highly unstable or has inherently transient character (e.g. pulsed from an ion trap or a pulsed ion source). Instead, they have identified that, to obtain an accurate estimate of the filling time of an ion trap, ideally a form of automatic gain control should take place concurrently with ion accumulation in the trap, and be representative of ion current at a particular instant. Moreover, the present inventors have realised that this objective can be achieved by intercepting a small portion of the incoming ion beam at suitable time intervals, which are substantially shorter than a characteristic time of variation of the ion current. In some typical examples, the time of variation of the current lies in the range of hundreds of microseconds. As such, the inventors have provided an improved, more precise method for controlling the filling of an ion trap with a predetermined quantity of ions.

(32) FIG. 2 shows an example having a number of features corresponding to the example of FIG. 1. In particular, the example of FIG. 2 shows a source of ions 10 and an ion trap 14. Ions from the source of ions 10 are transmitted along an ion path 18 and received by an ion trap 14. A detector 12 is capable of receiving ions transmitted from the ion source 10. However, in this example the detector 12 is an auxiliary detector, arranged external to the ion path.

(33) FIG. 2 further includes ion optics 20 arranged on the ion path 18, between the source of ions 10 and the ion trap 14. The ion optics 20 are configured to controllably direct (i.e. deflect) ions towards the detector 12 and away from the ion path 18 (see dashed arrow in FIG. 2). For instance, in this example, the ion optics 20 comprise a beam switching apparatus which can direct the ‘ion beam’ either towards the external ion detector 12 or to the ion trap 14, dependent on the potentials applied to portions of the beam switching apparatus.

(34) A controller 16 is arranged to be in communication with the detector 12 and the ion optics 20. The controller 16 is further arranged to control the operation of the source of ions 10 and the ion trap 14 (either directly, or through additional ion optics, not shown in FIG. 2).

(35) In use, the example of FIG. 2 operates in a similar manner to that of FIG. 1. In particular, ions are transmitted from the source of ions 10 over a transmission time period. During the transmission time period, the majority of the ions are received at the ion trap 14, and are accumulated therein. However, at distinct sampling time intervals interspersed within the transmission time period, ions are received at the detector 12. In this example, the ion optics 20 deflect the ions towards the detector 12 during the sampling time intervals. Over the transmission time period but outside of the sampling time intervals, the ion optics 20 allow the ions to proceed along the ion path 18 to the ion trap 14. The controller 16 may control this process through the application of appropriate voltages at the ion optics 20 to deflect the ions towards the detector 12 during the sampling time intervals.

(36) As in the example of FIG. 1, the ion current is varying in time. The frequency of the sampling time intervals is set to be sufficiently fast that the ions detected at the ion detector 12 reflect the variation in the ion current. In other words, the time difference between the start of a sampling time interval and the immediately subsequent sampling time interval is less than the timescale of the variation of the ion current.

(37) In the specific example of FIG. 2, the sampling time intervals are equal, each being 20 μs. An accumulation time interval (between the end of a sampling time interval and the start of a subsequent sampling time interval) is 80 μs. Thus, the time difference between the start of a sampling time interval and the start of the immediately subsequent sampling time interval is 100 μs. This is much less than the characteristic timescale of variation of the ion current, which in this specific example would be 200-500 μs for the RF ion guide of length L and the gas pressure P, wherein P×L>0.2 mbar mm. The overall transmission time period is 100 ms, with the total of the plurality of sampling time intervals making up 20% of the overall transmission time period. 1000 sampling time intervals are interspersed within the transmission time period.

(38) In the example of FIG. 2, a well-shielded Faraday cup is used as the detector 12. The Faraday cup is connected to a differential-input electrometer (not shown in FIG. 2) with a detection limit of 10,000-100,000 elementary charges. In most cases, 5 to 20% of the ions transmitted from the source of ions 10 during the transmission time period would be received at the Faraday cup by suitable selection of the sampling time interval. Therefore this design is especially suitable for filling ion traps with ion numbers in the range of 10.sup.5-10.sup.6 ions, such as required for the Orbitrap™ mass analyser. Nevertheless, if an electron multiplier of any type is used in place of the Faraday cup, then lower numbers of ions could be detected and a shorter sampling time interval (e.g. totalling 1-5% of the total transmission time period) could be used.

(39) FIG. 3 illustrates a method of controlling the filling of an ion trap with a predetermined quantity of ions. The method begins with the generation of an ion current by transmission of ions from a source of ions along an ion path (step 32). The path extends from the source of ions to an ion trap. Ions that traverse the ion path are received at the ion trap, and accumulate over a transmission time period (i.e. the time period over which ions can traverse the ion path). The magnitude of the ion current varies with time.

(40) In a second step (step 34), at least some ions from the ion source are detected at a detector. The ions are detected at the detector during a first, distinct sampling time interval.

(41) In a third step (step 36), ions from the ion source are received at the detector during at least one further distinct sampling time interval. The time difference, T, between the start of the further sampling time interval and the immediately preceding time interval is less than a timescale of variation of the magnitude of the ion current generated by the source of ions.

(42) In a fourth step (step 38), the duration of the transmission time period is set based on the detection of ions at the ion detector. For instance, this could be estimated from a fill rate determined from the ions detected during the first and any further sampling time intervals at the detector, or based on a comparison of the number of detected ions to a predetermined value.

(43) FIG. 4 illustrates a further example of the method of controlling the filling of an ion trap with a predetermined quantity of ions. Again, the method begins by generating an ion current by transmission of ions from a source of ions along an ion path (step 40). The path extends from the source of ions to an ion trap. Ions traverse the ion path over a transmission time period and can be received at the ion trap. The magnitude of the ion current varies with time.

(44) During a first sampling time interval within the transmission time period, at least some ions from the source of ions are detected at a detector (step 42). Subsequently, the duration of the transmission time period can be set (step 44). In particular, the transmission time period can be set based on the number of ions received at the detector during the sampling time interval. For instance the quantity of ions detected by the detector during the first time interval can be used to determine a filling rate for the ion trap, and so an estimate of the time for a predetermined quantity (or population) of ions to accumulate in the ion trap. Alternatively, the transmission time period can be terminated once the total number of ions received at the ion detector exceeds a predetermined amount. This disclosure is not limited to these methods of setting the transmission time, however. Other algorithms to estimate and set a transmission time based on the total quantity of detected ions received at the ion detector during the plurality of sampling time intervals would be apparent to the skilled person.

(45) The steps of detecting the ions at the ion detector can be repeated for a plurality of further sampling time intervals interspersed within the transmission time period (step 46). In particular, the step of detecting the ions at the ion detector and the subsequent step of setting the transmission time period based on the total quantity of detected ions received at the ion detector can be repeated N times within the transmission time. This will yield N+1 samplings of the ion current at the ion detector. It is noted that the value of N will depend on the transmission time set, and the time difference between the start of a sampling time interval and the subsequent sampling time period. The start of each sampling time interval is separated by a time difference, T, from the start of the immediate preceding sampling time interval. After elapse of each sampling time interval, the transmission time period can be set, as described above.

(46) In other words, the method comprises receiving at an ion detector at least some ions from the source of ions during an n.sup.th distinct sampling time interval, where 2≤n≤N+1 and nϵ. The start of the n.sup.th distinct sampling time interval is spaced from the start of the immediately preceding (i.e. n−1.sup.th) distinct time interval by a time difference, which is less than the timescale of variation of the ion current. After elapse of the n.sup.th sampling time interval, the duration of the transmission time period can be set based on the total quantity of ions received at the ion detector during the n.sup.th and each preceding sampling time interval. In this way, the transmission time is set in an iterative process.

(47) After elapse of the transmission time period, the transmission of ions along the ion path is interrupted (step 48). For instance, this could be by shut down or modulation of the ion source, or otherwise blocking or preventing the ions from entry to the ion trap.

(48) FIGS. 5A to 5G demonstrate measures of the timescale of variation of the ion current. It will be understood that the timescale of variation represents the average period over which the ion current changes significantly. For instance, it could be considered a characteristic time, which is an estimate of the order of magnitude of the time over which a change in the ion current occurs. The nature of the timescale of variation of the ion current will vary dependent on the particular ion source type, as well as any modulation of the ions whilst traversing the ion path. Rate of variation is typically dampened down by gas-filled radiofrequency (RF) ion guides as widely used in the art. A particular measure of the timescale of variation of the ion current can be selected based on its suitability in view of these parameters.

(49) In a first instance, the ion current may be varying approximately periodically. For instance, the ion current may increase and decrease periodically if the source of ions is a pulsed ion source (such as a laser or MALDI source). In this respect, the time period for variation of the ion current will be the average period of the ion current. This type of variation in the ion current is shown in FIG. 5A, with average period, or timescale of variation of the ion current, T.

(50) It should be noted that where the ion current is represented by periodic, distinct pulses (as illustrated in FIG. 5A) the timescale of variation can be considered the average pulse period, for instance. However, the time difference between the start of a sampling time interval and the immediately subsequent sampling time interval should then be chosen as not only less than this timescale of variation, but preferably much less (and ideally less than the width of the pulse). More preferably, the time difference between the start of a sampling time interval and the immediately subsequent sampling time interval should be much less than the rise- or fall-time of the pulse peak.

(51) In an alternative scenario, the ion current may be approximately constant. However, even the most stable ion sources have been shown to suffer from beam instability as well as noise up to many kHz. This instability can affect the ion filing rate at the ion trap, and thus in prior art methods risks overfilling the ion trap resulting in space-charge effects. Using prior art methods, a conservative filling time may be chosen to avoid space-charge effects, but this can result in a lower number of ions available for mass analysis.

(52) Where the ion current is approximately constant in this way, a timescale for variation of the ion current can be calculated as the average time difference between instances of the ion current being equal to the moving average magnitude of the ion current. For example, FIG. 5B illustrates a noisy and unstable ion current, with the moving average magnitude of the ion current shown as a dotted line. A time difference or period can be calculated between each instance of the ion current crossing the moving average. Each said time period is marked as T.sub.1, 2, 3, 4, . . . in FIG. 5B. The timescale of variation can then be calculated as the average of all T. In some circumstances, the median or the mean average may be appropriate. This measure of the timescale for variation of the ion current may also be used to determine the timescale for variation of the ion current for ion current which may or may not be approximately constant, and which exhibits step-wise changes, which exhibits periodic oscillations, or which exhibits aperiodic oscillations.

(53) Where the timescale for variation of the ion current is determined as the average time difference between instances of the ion current being equal to the moving average magnitude of the ion current, an appropriate base or window for the moving average must be selected. An appropriate selection of the time base may depend upon the ion source, and the ion optics and analyser used. In particular, the base for the moving average must be shorter than: (a) the average duration of ion accumulation prior to a scan, and/or (b) the duration of the scan (the transmission time period), and/or (c) the duration over which any voltages on the ion optics are kept constant. Nevertheless, the base for the moving average needs to be longer than (and preferably much longer than): (a) the temporal broadening during collisional cooling, and/or (b) the minimum gating time of the ion optics (or split or dual gate) arranged for injection of ions into trapped ion analysers (for instance linear ion traps or Orbitrap™ analysers), and/or (c) the average settling time of voltages on the ion optics (in other words, the shortest time of ion optics change). Moreover, the time base for the averaging should be longer (and preferably much longer) than the duration of a single sampling time interval, t (90 in FIG. 8).

(54) FIG. 5C shows an alternative behaviour for the variation of the ion current in time. In this example, the ion current reduces in time from a maximum ion current, I.sub.max. Here, the timescale for variation of the ion current can be defined as the time taken for the ion current to reduce by a predefined percentage of the maximum. In the particular example, of FIG. 5C, the timescale for variation of the ion current, T, is set as the time in which the ion current reduces to 60% of the maximum ion current, I.sub.max.

(55) FIG. 5D and FIG. 5E show a still further method of characterising the timescale of variation of the ion current. In this example, the ion current exhibits fluctuations due to noise consisting of multiple frequencies. Thus, the ion current is the sum of all signals, including multiple periodic noise signals (see FIG. 5D). To accurately estimate an appropriate filling time for the ion trap, the sampling frequency should be less than the fastest significant frequency within the noise spectrum. In this way, the sampling will resolve the variations in the ion current due to noise.

(56) In view of this, the timescale for variation of the magnitude of the ion current can be determined based on a Fourier transform of the ion current to the frequency domain. In particular, the timescale for variation of the ion current can be considered as the reciprocal of the frequency of a peak in a Fourier transform of the ion current, said peak being the highest frequency peak that exceeds a certain amplitude threshold. Looking to the present example, FIG. 5E shows the Fourier transform of the ion current in FIG. 5D to the frequency domain. Two significant peaks can be seen in the Fourier transform, as f.sub.1 and f.sub.2. Frequency f.sub.2 is higher than frequency f.sub.1. Here, the timescale of variation of the ion current can be defined as 1/f.sub.2.

(57) A further measure of the timescale for variation of the ion current can be considered where the ion current varies approximately stepwise. An example ion current is shown in FIG. 5F. It can be seen that the steps in the ion current are broadened or slightly smoothed compared to an ideal stepwise current. This may be a result of diffusion broadening, for instance due to use of a gas-filled RF ion guide along the ion path.

(58) FIG. 5G shows the derivative of the ion current with time. The derivative of an ideal stepwise function results in Dirac delta functions at the times representing the vertical portion of each step. However, due to the broadening in the real, approximately stepwise ion current, peaks can be seen at the time of each step in the ion current. The width of the peaks represent a timescale for the broadening of the stepwise ion current, and so a suitable timescale for variation of the ion current. For example, the mean average of the peak width at the full-width, half-maxima of each peak in the absolute value of the derivative can be used as the most general timescale for variation of the ion current. In relation to FIG. 5G, this would be the average of each of T.sub.1, T.sub.2 and T.sub.3.

(59) In a still further example, the timescale for variation of the ion current may be characterised by considering the autocorrelation of the ion current. As will be understood by the skilled person, autocorrelation describes the similarity (or correlation) between two instances in a signal as a function of the time lag or delay between them. In particular, the timescale of variation of the ion current may be considered as the mean average time lag between two observations of the ion current having an autocorrelation value of more than a predetermined value. For example, the average time lag between two observations having an autocorrelation value of more than 0.5.

(60) In some cases, an appropriate timescale of variation of the ion current may be known without investigation. For instance, this may be the case when a pulsed ion source is used, where the approximate period of the pulsed ion current would be apparent. However, in other scenarios, the timescale of variation may not be known prior to filling the ion trap. In this case, a pre-measurement of the ion current can be performed to determine the timescale of the variation in the ion current. For instance, the ion current may be measured continuously at an ion detector for a predefined period of time. The measured ion current in this period can then be analysed to determine the timescale for variation, according to one of the measures detailed above.

(61) Considering once again the examples of FIG. 1 and FIG. 2, the apparatus may be arranged to interrupt the ion current after elapse of the transmission time. For instance, the source of ions may be switched off or modulated, or the ions on the ion path may be blocked from entering the ion trap. This may require additional ion optics, not shown in FIGS. 1 and 2.

(62) FIG. 6 demonstrates a specific example in which the transmission of ions along the ion path 18 is interrupted by deflection of the ions from the ion path 18 to an ion dump 60. In this case, the ion optics 20 shown in FIG. 2 for intermittently directing ions to the detector 12 can also be used to direct (or deflect) ions to the ion dump 60.

(63) FIG. 6 shows a source of ions 10, which in use supplies ions along an ion path 18 towards an ion trap 14. Ion optics 20 are arranged on the ion path 18 between the source of ions 10 and the ion detector 12, such that at least a portion of ions can be deflected away from the ion path 18. In particular, the ion optics 20 can direct ions to either an auxiliary detector 12 (see dashed arrow in FIG. 6) or towards an ion dump 60 (see dashed-dot arrow in FIG. 6), dependent on the voltages applied at the ion optics 20. In particular, the ion optics 20 may comprise an ion gate, wherein applying a first voltage (or a zero voltage) causes the ions pass along the ion path 18 to the ion trap 14. Applying a second voltage to the ion gate causes the ions to be deflected off the ion path 18 towards the ion detector 12, as required during each sampling time interval. Applying a third voltage to the ion gate causes the ions to experience a different deflection (generally, a greater deflection) than compared to the period when the second voltage is applied, so as to instead move the ions towards the ion dump 14. Application of a third voltage in this way can be used to terminate the transmission of ions along the ion path 18, after elapse of the time transmission period.

(64) A further example in which the ion detector 12 is an electron multiplier is shown in FIG. 7. Here the ion detector 12 is a highly sensitive single-ion detector. Specifically, FIG. 7 shows a source of ions 10, from which ions are transmitted along an ion path 18, towards an ion trap 14. On the ion path 18 between the ion source 10 and the ion trap 14 is arranged an ion gate 20. An ion dump 60 is arranged to the side of the ion path 18, and a dynode 70 and detector of secondary particles 12 is arranged off the ion path 18, approximately opposite the ion dump 60. To avoid premature aging of the ion detector, ions that are dumped at the end of the transmission time period are deflected by the ion gate 20 to an ion dump in a direction approximately opposite to the detector.

(65) In use, with appropriate selection of applied voltages to the ion gate 20 the ions transmitted from the ion source 10 along the ion path 18 can be directed from the ion path 18 to either the ion trap 14, the detector 12 or the ion dump 60. For instance, the ions move along the ion path 18 when a first voltage is applied to the ion gate 20 (see solid arrow in FIG. 7). The first voltage is applied during the ‘accumulation intervals’, over which ions are accumulated at the ion trap 14.

(66) Upon application of a second voltage to the ion gate 20, the ions are deflected from the ion path 18 and in the direction of the dynode 70 (see dashed arrow in FIG. 7). Secondary particles generated by receipt of the ions at the dynode 70 can be directed to the detector of secondary particles or electron multiplier 12. The second voltage is applied during the sampling time intervals, in order to result in ions being received at the detector 12 during these intervals. In this way the detector of secondary particles 12 is used to ‘sample’ the ion current along the ion path 18. The frequency of the sampling time intervals (in other words, the time difference between the start of the application of the second voltage during a first sampling time interval and the start of the application of the second voltage in the immediately subsequent sampling time interval) is less than the timescale for variance of the magnitude of the ion current.

(67) Finally, after elapse of the transmission time period, a third voltage is applied to the ion gate 20, causing deflection of ions towards the ion dump 60 (see dot-dashed arrow in FIG. 7).

(68) In the examples of FIG. 6 and FIG. 7, it is particularly important that ions moving along the ion path do not experience deflection unless the ion gate 20 is activated. This can be achieved by applying an appropriate voltage to an electrode at the ion dump, in order to compensate for sag in the electrostatic field from the detector 12 and/or from the dynode 70. Alternatively a shielding grid could be used (not shown in FIG. 6 or FIG. 7).

(69) For inorganic ions, direct detection by a secondary electron multiplier (SEM) is possible and ion energies of 1-2 keV are sufficient for efficient detection. Any type of SEM could be used, for instance a channeltron, microchannel plates, a dynode, a dynode with scintillator and photomultiplier (PMT) or with a solid-state photomultiplier/avalanche diode, or even a combination thereof.

(70) For organic (and especially protein) ions, a separate conversion dynode is necessary. In this case voltage on the dynode typically exceeds 10 kV at a polarity opposite to the ion polarity (e.g. −10 kV for positive ions, +10 kV for negative ions). Once ions for detection are sufficiently diverted from their stable path, they are captured by the attracting field of the dynode and impinge on it, thereby producing secondary particles (specifically, ions and electrons). These secondary particles are then drawn towards the secondary particle detector by the attractive field of the detector, as would be understood by a person skilled in the art. In the detector they impinge on a conversion dynode, are converted into electrons and then multiplied using a secondary electron multiplier, in order to provide an indication of the ion current.

(71) FIG. 8 shows an example of the voltages that can be applied to the ion optics 20 (or ion gate) in FIG. 6. In particular, ions are transmitted along the ion path 18 to the ion trap 14 when a first constant voltage 82 (which may be zero, or close to zero) is applied at the ion gate 20. During these periods, in which a first voltage 82 is applied at the ion gate 20, the ions may be accumulated within the ion trap 14. In some circumstances, these periods can be denoted ‘accumulation intervals’ 76.

(72) According to the present example, a second voltage 84 can be applied at the ion gate 20 intermittently, for the period of a sampling time interval, t 90. The second voltage 84 is greater in magnitude (for instance, more negative) than the first voltage 82, and is approximately constant. During the sampling time interval, t (in other words, during the time when the second voltage 84 is applied to the ion gate 20), the ions from the ion source 10 are deflected from the ion path 18 and directed towards the ion detector 12.

(73) The second voltage 84 is applied on a plurality of occasions within the transmission time 80. In other words, the ion gate 20 is pulsed, with a square wave voltage pulse oscillating between the first voltage 82 and the second voltage 84. The period of the pulse is the time difference, T, 88 between the start of a sampling time interval and the immediately subsequent sampling time interval. The time difference, T, 88 could also be considered as associated with the sampling period, and consequently the sampling frequency. Accordingly, the time difference, T, is also the sum of a sampling time interval, t, 90 and an accumulation interval 76. A number, N, of pulses with period, T, can be applied within the transmission time period 80 (note that only three pulses are shown in FIG. 8, for clarity). The time difference, T, is less than (and preferably much less than) the timescale of variation of the magnitude of the ion current, T, as described above with reference to FIGS. 5A to 5G.

(74) At the end of the transmission time period 80, a third voltage 86 can be applied at the ion gate 20. The third voltage 86 is greater in magnitude (for example, more negative) than the second voltage 84, and causes the ions to be deflected further from the ion path 18 than compared to the transit of ions during the sampling time intervals, t (under the second voltage 84). Instead, during a period 92 when the third voltage 86 is applied, the ions are directed towards the ion dump 60. Thus, these ions are not accumulated at the ion trap 14, nor received at the ion detector 12. In this way, application of the third voltage 86 terminates the transmission of the ions along the ion path 18.

(75) In the particular example of FIG. 6, the first voltage 82 applied at the ion gate is −50V, the second voltage 84 is −150V and the third voltage 86 is −350V. The first voltage 82 is applied for a period of 90 μs, between periods of application of the second voltage 84 for 10 μs. Accordingly, together this represents a high-frequency pulse having a period 88 of 100 μs (or frequency of 10 kHz). This period for the sampling of the ion current (in other words, the time difference between the start of a sampling time interval and the start of the immediately subsequent sampling time interval 88) is selected to be less than the time scale of variance of the ion current.

(76) The transmission time period 80 is 100 ms, such that 1000 pulses (for instance, 1000 cycles of the application of the first and second voltages) are applied within the transmission time period 80.

(77) Considering FIG. 8, it can be seen that the periods of application of the second voltage, interspersed between periods of the first voltage, represent a high frequency square wave voltage pulse applied at the ion gate. In other words, the gate is pulsed at high frequency. Where ion guides are arranged nearby to the pulsed ion gate (as would be customary when the examples of FIG. 2, FIG. 6 or FIG. 7 are incorporated into various mass spectrometer configurations) the high frequency pulse applied at the ion gate can result in perturbation at the ion guide and subsequent noise on the ion current. For reduction of this noise, a measurement of the offset to the ion current is introduced. The offset to the ion current created by the background noise within the system can be subtracted from each signal at the ion detector. As a result, currents in the femtoampere range and total charges in the femtocoulomb range can be detected at the ion detector.

(78) An example of the electronic circuitry used to first determine the offset to the ion current due to noise, and then subtract this offset from a measured ion signal, is shown in FIG. 9. This circuitry may be especially useful when used together with the examples of direct current measurement of FIG. 2, FIG. 6 and FIG. 7. Nevertheless, such circuitry may also advantageously be applied to prior art systems for automatic gain control (where there is a pre-measurement of the ion current performed prior to acquisition of ions by a mass analyser).

(79) As such, FIG. 9 shows a simplified diagram of an electrometer 900 for use in measuring the ion current of the deflected ion beam. The ion optics, as described above with reference to FIGS. 2, 6 and 7, are used to deflect the ion beam 89 prior to measurement. In FIG. 9, the ion optics include a deflector electrode 93 and a lens electrode 94. In parallel to the deflector 93 and lens 94 electrodes, there are first and second detection electrodes, Det+ 95 and Det− 96, respectively. In use, a deflector control signal 87 is applied to the deflector electrode 93, thereby causing the ion beam 89 to be deflected towards the first detection electrode Det+ 95. The charge subsequently received at the first detection electrode Det+ 95 is then measured using a charge-to-digital converter 97. As discussed above, the ion beam is intermittently deflected (being deflected only during the sampling time intervals 90) and so the deflector control signal 87 is effectively a pulsed signal, as shown in FIG. 8.

(80) The electrometer 900 has a symmetrical structure, wherein the second detection electrode Det− 96 is associated with a corresponding charge-to-digital converter 98. This symmetrical structure allows elimination of symmetrical pickup noise, for example from power source 99 connected to the detection electrodes 95, 96. Such a power source (which may generate a signal affected by high frequency noise, for example) would induce equal charge as a result of noise on both the first and second detection electrodes 95, 96.

(81) Despite partial electrostatic shielding between the deflector 93 and the first and second detection electrodes, Det+ 95 and Det− 96 respectively, a voltage pulse applied to the deflector 93 during the sampling time interval 90 can induce some charge on the detecting electrodes 95, 96 as a result of crosstalk 91. As a result, the induced charge as a result of crosstalk may distort the useful measured signal.

(82) The magnitude of the induced charge as a result of crosstalk is lower on the second detection electrode Det− 96 (as a result of its greater distance to the deflector electrode 93 compared to first detection electrode Det+ 95). Therefore, for achieving full compensation of the crosstalk effect, a portion 85 of the deflector control signal 87 is applied to the second detection electrode Det− 96 through a controlled attenuator 83.

(83) The electrometer 900 contains identical first and second charge-to-digital converters 97, 98, each consisting of an integrator 971, a comparator 972, a reference voltage switch 973 and an impedance means 974, through which a compensating charge is fed to the input of the integrator 971. As will be understood by the skilled person, although only the first charge-to-digital convertor 97 shows these components in FIG. 9, corresponding components are implemented in the second charge-to-digital convertor 98.

(84) The digital signal output 975 from first charge-to-digital converter 97 is subtracted from the digital signal output 985 of second charge-to-digital converter 98 in the logical control block 910. As such, noise on the detection signal measured at first detection electrode Det+ 95, where it has been induced symmetrically on both the first and second detection electrodes, Det+ 95 and Det− 96 respectively, may be cancelled. Subsequently, the output digital signal, representative of the noise cancelled detected ion current, is transmitted from the control block 910 to a processor (not shown) via the control bus 912.

(85) The above described examples (for instance, at FIG. 1, FIG. 2, FIG. 6 or FIG. 7) can be located in high vacuum (<1e.sup.−3 mbar) area of a mass spectrometer. The ion current generated may be considered as (quasi-) continuous. The described embodiments can be incorporated into a wide array of mass spectrometer apparatus. Examples of the source of ions may include any one of: an ion source (such as electrospray ionisation (ESI) or matrix-assisted laser desorption/ionization (MALDI)); an atmosphere-to-vacuum interface; an ion guide; a mass analyser or ion mobility analyser; or an ion trap. The described examples may be used to control ion filling of an ion trap of any type, with or without gas, including but not limited to: a radio-frequency (RF) trap (quadrupole, linear, etc.); a Penning trap; an electrostatic trap (e.g. Orbitrap™ analyser); or a time-of-flight trap. The described examples could be also installed between ion traps.

(86) FIG. 10 illustrates a preferred example, in which the invention is employed within a quadrupole-orbital trapping mass spectrometer 100 (such as an Orbitrap™ analyser). The quadrupole-orbital trapping mass spectrometer 100 depicted incorporates an ion source 110, a quadrupole ion mass filter 124, a curved ion trap (or C-trap) 114, a higher-energy collisional dissociation (HCD) cell 126, an orbital trapping mass analyser 128 and a digital-to-analogue converter 130. Arranged between the quadrupole ion filter 124 and the curved ion trap (or C-trap) 114 (and therefore between the ion source 110 and the curved ion trap 114), is apparatus 122. Apparatus 122 represents the portions of either FIG. 1, FIG. 2, FIG. 6, or FIG. 7 in marked area 22 of these Figures. Apparatus 122 includes the ion detector 12, in some examples together with ion optics 20 and an ion dump 60. In other words, apparatus 122 represents the configuration of the ion detector required to implement the invention described herein. In addition, to the components shown in FIG. 10 of mass spectrometer 100, various ion optics (not shown in FIG. 10) may be implemented to guide and focus the ion beam though the mass spectrometer.

(87) In use, over a transmission time period ions from the ion source 114 are transmitted along an ion path 118 through the quadrupole ion filter 124, via the apparatus 122, to the C-trap 114 where they are accumulated together. This provides an ion current which is inherently varying in time. Subsequent to the elapse of the transmission time period, in order to obtain a fragment ion mass spectrum (MS2 spectrum), the accumulated ions are passed from the C-trap 114 to the HCD cell 126 for fragmentation. The ions are then returned to the C-trap 114 before injection into the mass analyser 128, in order to perform an analytical scan. In some embodiments, the ions may be transmitted (without trapping) through the C-trap 114 to the HCD cell 126 for fragmentation or cooling and then returned to the C-trap where they are finally trapped. In order to obtain a precursor ion mass spectrum (MS1 spectrum), the accumulated ions are injected from the C-trap 114 into the mass analyser 128 without fragmentation in the HCD cell 126, in order to perform an analytical scan.

(88) The apparatus 122 includes an ion detector which intermittently detects (or samples) the ion current (as described above with reference to FIG. 1, FIG. 2, FIG. 6 or FIG. 7). Specifically, the ions are detected at the ion detector during a plurality of sampling time intervals. The time difference between a sampling time interval and the start of the subsequent sampling time interval (related to the sampling frequency) is set to be less than the timescale of variation of the ion current. In this way, the detector can monitor the ion current, in order to accurately predict the quantity of ions received at the C-trap 114. Accordingly, the C-trap 114 can be filled to the maximum ion population allowed without exceeding the space-charge limit.

(89) It is noted that in this example, the C-trap 114 is filled with bath gas up to 1e.sup.−3 mbar. Thus, collisional fragmentation of ions can be expected to occur. In order to avoid this, an additional short radio frequency-only multipole (5-15 mm long) (not shown in FIG. 10) can be inserted between the detector exit and C-trap entrance. Furthermore, in this case an ion lens forming part of the ion optics shown in FIG. 2, FIG. 6 or FIG. 7 could also be used as shields to reduce radio frequency penetration or noise at the sensitive detector circuitry.

(90) FIG. 11 shows the signal-to-noise ratio of ions measured by an orbital trapping mass analyser in a mass spectrometer of the type shown in FIG. 10. The signal-to-noise ratio is plotted versus the ion current measured by an electrometer for different mass-to-charge ratio (m/z). The data was measured incorporating the noise reduction circuitry of FIG. 9. As can be seen in FIG. 11, differences in the stability of the measured current resulting from the different mass-to-charge ratios of the ions can be compensated for by the use of the described examples, as confirmed by the resulting linear relation between the current measured by the electrometer and signal-to-noise ratio acquired by the Orbitrap™ analyser.

(91) To avoid m/z-dependant bias in mass spectra, it is preferable to perform calibration of the above-described method using compounds of different m/z and then correct subsequently acquired mass spectra.

(92) Many combinations, modifications, or alterations to the features of the above embodiments will be readily apparent to the skilled person and are intended to form part of the invention. Any of the features described specifically relating to one embodiment or example may be used in any other embodiment by making the appropriate changes.

(93) Although not necessarily shown in the specific examples above, it will be understood by the skilled person that a variety of additional ion optics may be employed in order to gate, filter or otherwise control the ion beam in the apparatus and in particular ions traversing the ion path. For example, beam focussing lenses may be employed.

(94) In addition, a gas-filled ion guide may be employed prior to the ion trap. Ions from an ion source (such as an electrospray ionisation source (ESI) or matrix-assisted laser desorption/ionization ion source (MALDI)) may be transmitted to the ion trap via the gas-filled ion guide. In this example, passage through the gas-filled ion guide can result in broadening of any changes in the ion current. For example, diffusional broadening can result in ‘smoothing’ or broadening of any step changes in the ion current. In this example, the characteristic time of variation of the ion current is affected by said diffusional broadening. Thus, the ion detector should be arranged subsequent to the gas-filled ion guide (but before the ion trap), and the time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval should take into account the diffusional broadening.

(95) In the above examples, a number of specific types of ion detector are discussed. Nevertheless, it will be understood by the skilled person that various types of ion detector can be used within the configurations described. For instance, the ion detector may be (but is not limited to) a Faraday cup, a single-ion detector, secondary electron multiplier, an electrometer, an ion-to-photon detector, a microchannel plate detector, or another type of electron multiplier.

(96) Similarly, it will be understood that the invention is not limited to use of any particular type of ion source described above. The invention requires a source of ions which may be any apparatus and device which can provide or supply ions to the ion path. The ions may be generated at the source of ions, or merely stored and transmitted therefrom. Accordingly, the types of ion source for use with the invention may include any of an ion trap, an ion source, an electrospray ionisation source (ESI), matrix-assisted laser desorption/ionization ion source (MALDI), a mass analyser, or an ion mobility analyser.

(97) Moreover, the type of ion trap used within the invention may be of any type, and is not limited to those discussed with reference to the examples above. For instance, the ion trap may be one of a radio frequency trap (for instance, a quadrupole ion trap cylindrical ion trap or a linear quadrupole ion trap), a Penning trap, an electrostatic trap, a time of flight trap, or a curved trap.

(98) Finally, although the invention is discussed specifically with reference to an orbital trapping mass analyser in relation to FIG. 9, it will be understood that the invention could be used in conjunction with any type of mass analyser. For instance, the present invention may be used within a time-of-flight mass spectrometer, a quadrupole mass spectrometer, a sector field mass spectrometer, or a Fourier transform ion cyclotron resonance mass spectrometer.