Mass spectrometer and method for calibrating the same

Abstract

To provide a method for checking calibration of a dual mode secondary electron multiplier (SEM) detector of a mass spectrometer using non-analyte ions.SOLUTION: A method includes the steps of: recording, using a counting mode detector of a dual mode SEM detector, a first counting signal associated with the number of non-analyte ions incident on the SEM detector at an operating point voltage; offsetting an operating point of the counting mode detector and recording a second counting signal associated with the number of non-analyte ions incident on the SEM detector at respective two or more offset operating point voltages; fitting a non-linear function to a first and a second recorded counting signals and a value corresponding to the operating point voltage; and determining that calibration is valid if a rate of change in the non-linear function at the calibrated operating point is within an acceptable range. A mass spectrometer configured to perform the method.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a secondary electron multiplier (SEM) detector such as used to detect ions emerging from a mass analyzer of a mass spectrometer. In particular, the present invention relates to the calibration of such detectors and the checking of existing calibrations of the detectors.

Background Art

[0002] Mass spectrometry is a series of techniques for the identification and quantification of species in a substance. Elemental mass spectrometry is one branch of mass spectrometry where it is desirable to determine the type and amount of chemical elements present in a sample. A wide dynamic range is required or at least beneficial for accurate measurements.

[0003] A secondary electron multiplier (SEM) detector is a type of detector having a surface coated with a secondary electron emitting material. When electrons collide with the secondary electron emitting material, secondary electrons are emitted. If a plurality of such structures are cascaded one after another, the generation of secondary electrons is repeated and the number of electrons can increase by millions of times. Such a detector may be known as an electron multiplier detector. One type of mass spectrometry using such a detector is inductively coupled mass spectrometry (ICP-MS).

[0004] To achieve a wide dynamic range, the SEM detector may be a dual-mode detector having two operating modes, namely a counting or pulse mode and an analog mode. The counting mode may provide a dynamic range of 10 6 and the analog mode may provide an additional three to four orders of magnitude of dynamic range. Usually, the two operating modes have a range of overlap to enable one mode to be calibrated against the other. Some systems have an additional potentiometer mode that provides an additional three to four orders of magnitude of dynamic range, which is achieved by directly measuring the ion beam using a Faraday cup.

[0005] Further details of the structure of the dual-mode SEM ion detector are schematically shown in FIG. 1. The ion detection device includes a series of dynodes shown as D1 to D8 and a detector T1. An ion beam I incident on the first dynode D1 is converted into one or more electrons. This first dynode is sometimes known as a conversion dynode since it converts incident ions into electrons. The dynodes are negative and under an appropriate potential that increases (approaches ground) as it moves from the first dynode D1 to the last dynode D8. The figure shows eight nodes, but other numbers of dynodes may be used. One or more electrons generated by the first / conversion dynode are accelerated by the potential towards the next dynode. At each subsequent dynode, the collision of electrons at the dynode generates one or more secondary electrons and attracts them to the next dynode again. As a result, a cascade occurs in which the number of electrons increases. For example, for a single electron reaching D1, millions of electrons may be incident on the detector T1. The detector T1 can collect electrons and convert them into a voltage or current that forms an output signal. For the detector T1 following the last dynode, the output signal is a pulse or count signal S c known as. The amplification provided by the series of dynodes is large. When the number of ions entering the detection device is relatively large, the number of electrons reaching the detector T1 can be more than the maximum detectable signal that can be accommodated by the dynamic range of the detector. As shown in FIG. 1, the analog signal S A A second output signal known as may be output midway along the series of dynodes. For example, in FIG. 1, the analog signal is derived from the fifth dynode out of eight dynodes. Generally, the dynode providing the analog signal is midway along the series of dynodes, for example, a dynode in the middle of the series of dynodes. At the fifth dynode, the amplification of the number of electrons is not as large as that of the eighth dynode. Therefore, for a larger number of input ions, the analog signal will continue to provide an output signal, thereby increasing the dynamic range beyond that for the pulse / count signal alone.

[0006] In the case of inductively coupled plasma mass spectrometry (ICP-MS), for example, the detection device should be able to operate over a nine-digit dynamic range, preferably more. This is to enable the detection device to detect the main and minor components of the sample.

[0007] As described in the previous paragraph, the two detection modes can be calibrated against each other within the range where both detectors operate. Once calibrated, the system should deliver reliable quantitative output for days, weeks, or even months depending on the intensity of use. However, the problem with dual-mode SEM detectors is the drift in amplification factor due to the aging effect of the dynode surface material.

[0008] U.S. Patent No. 5,463,219 and U.S. Patent No. 11,469,091 (B1) describe a dual-mode secondary electron multiplier detector used in a mass spectrometer. UK Patent Application Publication No. 2421841 describes a method for cross-calibrating between a counting mode detector and an analog mode detector of a secondary electron multiplier. SUMMARY OF THE INVENTION

[0009] The present invention provides a fast method for checking whether the existing calibration of a counting mode detector remains accurate. The method also provides a fast method for checking the cross-calibration between a counting mode detector and an analog mode detector, and a method for re-calibration. These methods can be performed by a mass spectrometer instrument during background or idle time without the need for user input. The method may use argon ions derived from argon as the carrier gas used to generate sample ions and flow them through the spectrometer. Argon may be flowed through the spectrometer when no sample is present, and thus the calibration check and calibration may be performed without the need for a calibration sample or solution. Argon and / or other non-analyte gases may be used.

[0010] The present invention is a method for checking the calibration of a dual-mode secondary electron multiplier (SEM) detector of a mass spectrometer using non-analyte ions, comprising setting the counting mode detector of the SEM detector to a calibrated operating point by providing an operating point supply voltage to the counting mode detector; recording a first counting signal based on the number or amount of non-analyte ions incident on the SEM detector using the counting mode detector; offsetting the operating point of the counting mode detector by adjusting the supply voltage to the counting mode detector; recording a second counting signal at each one, two, or more offset supply voltages related to the number or amount of non-analyte ions incident on the SEM detector using the counting mode detector; fitting a non-linear curve or function to the first and second recorded counting signals and the values corresponding to the counting mode detector supply voltage; and determining that the calibration is valid if the rate of change of the non-linear curve at the calibrated operating point is within an acceptable range. The term "non-analyte ions" means ions that are not the analyte, i.e., ions that are not part of the sample being analyzed. Non-analyte ions may include ions used to flow the sample through the analyzer, such as carrier gas ions or carrier ions. Non-analyte ions may include argon ions, which may be derived from the carrier gas and / or plasma gas. Non-analyte ions may additionally or alternatively include calibration substance ions generated from a calibration solution. The term "non-analyte ions" includes a plurality of ions. Typically, the plurality of ions includes carrier gas ions but does not include calibrant ions.

[0011] The counting signal referred to herein may be related to the count number detected by the counting mode detector over a period such as one second, or the count number averaged over such a period. The counting may be the actual counting of incident electrons, the detection of charged particles, or the accumulation of voltage. The use of curve fitting allows for a quick determination of whether the operating point has moved and requires adjustment, as well as the amount and direction of adjustment that may be required. In particular, curve fitting typically allows for the determination of the amount and direction of adjustment without the need for additional offset operating point voltages.

[0012] Adjusting the supply voltage to offset the operating point of the counting mode detector includes offsetting the operating point to a first offset operating point at a voltage higher than the operating point voltage and offsetting the operating point to a second offset operating point at a voltage lower than the operating point voltage. Recording the second count signal at each of two or more offset operating point voltages may include recording an upper second count signal at the first offset operating point voltage and recording a lower second count signal at the second offset operating point voltage. Alternatively, the second count signal may be measured at one offset operating point or two or more offset operating points. In embodiments, all of the offset operating points may be at voltages higher or lower compared to the operating point voltage. The operating point voltage means the voltage at which the detector is operating for analysis and is determined, for example, through a previous calibration or preset by other means.

[0013] The tolerance range may be a tolerance range normalized with respect to the count signal at the calibrated operating point.

[0014] The normalized tolerance range may be a rate of change of less than 5%, 10%, or 15% of the non-linear curve at the calibrated operating point.

[0015] The non-linear curve may be a quadratic polynomial.

[0016] The method may further include estimating a supply voltage at which the rate of change of the non-linear curve is within the tolerance range based on the non-linear curve or function, based on determining that the rate of change of the non-linear curve at the calibrated operating point is not within the tolerance range, and adjusting the operating point to the estimated supply voltage.

[0017] This method can further include recording a first count signal updated in a count mode detector with the operating point changed to an estimated supply voltage, re-fitting a non-linear curve or function to data including the first count signal, a second count signal, and the updated first count signal at the estimated supply voltage, and determining whether a rate of change of the non-linear curve or function at the estimated supply voltage is within an acceptable range.

[0018] Based on the non-linear curve or function, the step of estimating the supply voltage at which the count signal is within the acceptable range can include estimating the supply voltage at which the rate of change of the non-linear curve or function is at a target value within the acceptable range. The target value may be the midpoint of the acceptable range.

[0019] The method can further include providing the user with a warning requesting that the user perform recalibration of the count mode detector based on determining that the rate of change of the non-linear curve or function at the calibrated operating point is not within the acceptable range.

[0020] This method can include performing recalibration of the count mode detector when it is determined that the calibration is not valid.

[0021] Recalibration of the count mode detector can include offsetting the operating point of the count mode detector by adjusting the supply voltage to the count mode detector to one or more second offset voltages, using the count mode detector to record a third count signal at each of the one or more second offset operating point voltages based on the number or amount of non-specimen ions incident on the SEM detector, fitting a second non-linear curve or function to the values corresponding to the first, second, and third recorded count signals and the count mode detector supply voltage, and estimating the supply voltage at which the rate of change of the second non-linear curve or function is within a second acceptable range based on the second non-linear curve or function and adjusting the operating point to the estimated supply voltage.

[0022] The second non-linear curve may be a cubic polynomial.

[0023] The second tolerance range may be a change rate of less than 5%, 10%, or 15% of the non-linear curve at the operating point.

[0024] The method may further include recording an analog signal in an analog mode detector of a dual mode secondary ion detector, calculating a mutual calibration coefficient between the analog mode detector and the counting mode detector based on a first count signal and the analog signal at the operating points of the counting mode detector and the analog mode detector, and determining that the mutual calibration is valid when the mutual calibration coefficient is within a window or within a target calibration coefficient.

[0025] The method can include performing a correction of the mutual calibration measured between the counting mode detector and the analog mode detector when it is determined that the mutual calibration is not valid.

[0026] Cross-calibration correction includes recording a first analog mode signal related to the number or amount of non-specimen ions incident on the SEM detector using the analog mode detector at the analog mode detector operating point supply voltage; recording a first cross-calibration count mode signal as the number or amount of non-specimen ions incident on the SEM detector using the count mode detector at the count mode detector operating point supply voltage; offsetting the operating points of the analog mode detector and the count mode detector by adjusting the supply voltages to the analog mode detector and the count mode detector; using the analog mode detector and the count mode detector to record a second analog mode signal and a second cross-calibration count mode signal related to the number or amount of non-specimen ions incident on the SEM detector at the adjusted supply voltages; repeating the process of offsetting and recording a further second analog mode signal and a further second cross-calibration count mode signal; determining cross-calibration coefficients for the first analog mode signal, the second analog mode signal, the further second analog mode signals, and the count mode signals; fitting a third non-linear curve or function to values corresponding to the first, second, and further second analog mode signals and the operating point voltage of the analog mode detector; estimating an analog detector supply voltage at which the cross-calibration coefficients are within an acceptable range or meet a target based on the third non-linear curve or function; estimating a count mode detector supply voltage for the acceptable range or target based on the estimated analog detector supply voltage at which the cross-calibration coefficients are within the acceptable range or meet the target; and adjusting the operating point voltages of the analog mode detector and the count mode detector to the estimated supply voltages.

[0027] The non-specimen ions may be argon ions, noble gas ions, or nitrogen ions.

[0028] The method described herein may be implemented using non-specimen ions without a calibration solution.

[0029] The method may be performed before analyzing a sample and / or in the background without warning the user.

[0030] This method may be executed at regular intervals in the background without warning the user.

[0031] A method for checking the cross - calibration of a dual - mode secondary electron multiplier (SEM) detector of a mass spectrometer using non - analyte ions, the method comprising: setting the counting - mode detector of the dual - mode SEM detector to a calibrated operating point by providing an operating - point supply voltage to the counting - mode detector; setting the analog - mode detector of the dual - mode SEM detector to a calibrated operating point by providing an operating - point supply voltage to the analog - mode detector; recording a counting signal related to the number of non - analyte ions incident on the SEM detector using the counting - mode detector; recording an analog - mode signal related to the number of non - analyte ions incident on the SEM detector using the analog - mode detector; calculating a cross - calibration coefficient between the analog - mode detector and the counting - mode detector based on the counting signal and the analog - mode signal; and checking whether the cross - calibration coefficient is within a window or within a target calibration coefficient.

[0032] The present invention provides a method for checking the calibration of a dual - mode secondary electron multiplier (SEM) detector of a mass spectrometer, the method comprising: obtaining a first counting signal from a counting - mode detector at an operating - point voltage, the first counting signal being related to the number or amount of non - analyte ions incident on the SEM detector; obtaining a second counting signal related to non - analyte ions at one, two, or more offset operating - point voltages of the counting - mode detector; fitting a non - linear curve or function to the first and second counting signals and values corresponding to the counting - mode detector supply voltage; and determining that the calibration is valid when the rate of change of the non - linear curve at the calibrated operating point is within an acceptable range.

[0033] A computer - readable medium storing instructions that, when executed by a processor, cause the processor to execute the aforementioned method.

[0034] A mass spectrometer comprising a dual-mode secondary electron multiplier (SEM) detector configured to perform any of the methods described herein.

[0035] Hereinafter, embodiments of the present invention and aspects of the prior art will be described with reference to the accompanying drawings.

Brief Description of the Drawings

[0036]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

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Figure 8

Figure 9

Figure 9a

Figure 10

Figure 11

Figure 12

Figure 13

Figure 14

DETAILED DESCRIPTION OF THE INVENTION

[0037] As described above, FIG. 1 is a schematic diagram of a dual-mode detector that may include, for example, a plurality of dynodes. The voltage of the first / conversion dynode is negative and relatively high. The voltage on the subsequent dynodes increases while remaining negative but decreasing in magnitude. The voltage on the dynodes after the series may be positive and gradually becomes positive towards the end of the series of dynodes. The voltage difference between consecutive dynodes may be the same. In some embodiments, the voltage difference between the first two dynodes may be higher than that between other dynodes. In some embodiments, the voltage difference may increase sequentially for the subsequent dynodes. The following table provides exemplary voltages for a dual-mode detection device having eight dynodes as shown in FIG. 1. The table also includes the voltage at the detector T1 which is positive. Thus, the detector T1 may be considered as the anode of the detection device. The values given in the following table are exemplary voltages for a positive ion dual-mode detector without a separate conversion dynode. The ion is converted to secondary electrons at a potential of -Ua on the first detector dynode. For negative ion detection or the use of a separate conversion dynode, the voltage at the dynode and the resulting potential landscape are different. However, the checking and calibration methods described here can also be applied in a similar manner.

[0038]

Table 1

[0039] Increasing the magnitude of the voltage on the dynode and detector T1 tends to increase the amplification of the number of electrons such that the gain in the analog and pulse counting signals is increased. However, the dynode may be more likely to age more rapidly when held at a higher magnitude of voltage. This may be due to the effect of aging on the surface material of the dynode.

[0040] Figure 2 is a schematic graph of the detector supply voltage versus the normalized count rate. The abscissa represents the total detector supply voltage. That is, the sum of the magnitudes of the voltages in the analog detector and the pulse counting or counting mode detector. In more general positive ion detection, the voltage at the entrance to the detector is negative, pulling the positive ions into the detector. Thus, the voltage in the analog detector is usually negative. The electrons continue to be amplified towards the counting detector. The counting detector has a positive voltage. The sum of the voltages from the analog detector to the counting detector can be written as follows. |-Ua|+Uc Here, Uc is the voltage in the counting detector, and Ua is the voltage in the analog detector. Since Ua is usually negative, its magnitude is taken here for obtaining the sum. The total value is a measure of how strongly electrons are accelerated from the analog detector to the counting detector dynode surface, and thus, a measure of the amount of secondary electrons that are likely to be generated. Returning to FIG. 2, the vertical axis is a measure of the pulse / counting detector count rate at each detector voltage, normalized with respect to the pulse / counting detector count rate at the operating point voltages of the analog and counting detectors. By definition, in the schematic curve, the count rate at the operating point WP voltage is 1. At lower voltages, the count rate decreases at a decreasing rate, while at higher voltages, the count rate increases but only very slowly. This is due to the fact that in a well-calibrated WP, very few electron pulses remain above the detection threshold of the detection system. A well-calibrated WP is characterized by the detection of >90% of all electron pulses generated by the ions incident on the detector.

[0041] We previously described that the aging deterioration of dynodes can change the amplification factor. Figure 3 shows how the aging deterioration of the dual-mode SEM detector brings about a gain curve shift and how it brings about an operating point shift. The shape of the gain curve remains substantially the same as the aging deterioration of the detector, but the operating point and a specific gain require an increasing voltage. Similar to Figure 2, the abscissa in Figure 3 indicates the total detector voltage |-Ua|+Uc (written as Uc-Ua in the figure) applied to the dynode to which the detector is connected, where Uc is the voltage at the counting dynode and -Ua is the voltage at the analog detector. The ordinate indicates the normalized counting rate, that is, the counting rate (measured in the pulse / count detector T1) in the range of the total voltage, normalized with respect to the signal at the operating point when Uc-Ua is at the operating point. Figure 3 shows four measured gain curves. The data points measured for each of the different curves are represented as squares, diamonds, circles, and triangles, respectively. The curve with the data points represented by squares has the smallest amount of aging deterioration and the lowest total voltage. In this curve, the operating point is approximately 3950V. The curves with the data points represented by diamonds, circles, and triangles are for longer aging deterioration and longer aging deterioration, respectively. The operating points are approximately 4050V, 4150V, and 4210V, respectively.

[0042] To determine the operating point, the total detector supply voltage is varied and the corresponding change in counting in the counting detector is analyzed. In the case of a dual-mode detector having a supply voltage Ua for the analog detector and a supply voltage Uc for the counting detector, the operating point is defined by the plateau criterion. This criterion checks the slope of the gain curve at the operating point. Ideally, the operating point is at the total voltage where the gain is maximum. However, as schematically shown in Figure 2 and also seen in Figure 3, the gain becomes almost flat at a higher supply voltage, but it continues to increase slightly. Therefore, a simple algorithm for maximizing the gain would be to push up the detector supply voltage to a high level, which may cause the aging deterioration of the detector. Therefore, it is preferable that the operating point voltage is set at the point where the sharp increase in gain slows down with an increase in the supply voltage.

[0043] The plateau criterion is used to check that the gain slope at the operating point heads towards the plateau of the curve where the gain approaches its maximum. The criterion is characterized by requiring that the signal loss when the detector supply voltage is reduced be within an acceptable range, by checking that the operating point is as close as possible to the maximum. In other words, the plateau criterion checks that the operating point is set near the plateau. If the operating point is away from the plateau and under the steeper part of the decreasing signal gradient, a given change in the supply voltage away from the operating point will result in a large decrease in the signal. Since the detector type and the signal vary, the signal change is normalized with respect to the signal at the operating point. As described above, the operating point voltages of the counting detector and the analog detector may be Uc and -Ua respectively. The change in the operating point voltage is given by ΔU. The plateau criterion can be defined by the following equation.

[0044]

Number

[0045] Figure 4 shows the variation of the signal with respect to a range of operating points. The nominal operating point voltage (Uc + |-Ua|) is set to approximately 3950V, which is identified in the figure as the signal at 100%. For changes in the operating point voltage supplied to the detector of + / -100V, i.e., to 3850V and 4050V, the variation of the signal count is determined. For a -100V change in the supply voltage, the signal drops to 87% of the signal at the nominal operating point. This is written as a change of 0.129 according to the above formula and meets the criterion of being less than 0.15. For a +100V change in the supply voltage, the value of the above formula is -0.04, which also meets the criterion of being less than 0.15. This is shown on the graph as the normalized signal increasing to 104% of the signal at the operating point. Therefore, at an operating point voltage of 3950V, the detector is operating meeting the plateau criterion. In the criterion, the response becomes significantly flat, and as a result, the count rate hardly increases beyond 105% as a whole in the context of the graph even at a supply voltage of 4250V. Therefore, when the voltage is set to the WP value, more than 90% of the pulses are detected.

[0046] Alternatively, since much of the variation of the signal depends on the operating point of the counting detector, when checking and adjusting the operating point of the counting detector, only Uc can be changed while keeping Ua fixed. Therefore, the plateau criterion can be described based only on the variation of the signal due to the supply voltage to the counting detector. If Pc(Uc) is the formula that defines the signal as a function of the supply voltage to the counting detector, the plateau criterion can be written as follows.

[0047]

Number

[0048] FIG. 5 is a flow diagram showing a method according to an embodiment of the present invention that uses a plateau criterion to check the operating point of a counting detector. The method includes setting a counting mode detector and an analog mode detector to their operating point voltages, and in step 110, measuring signal Sc in the counting mode detector and measuring signal Sa in the analog mode detector. Although signal Sa in the analog mode detector is not required for plateau checking, it may be needed later for cross-calibration checking between the two detectors, so it is useful to measure it at this point. In step 120, the supply voltage to the counting mode detector is adjusted by + / -ΔU, and the respective counting mode signals Sc(Uc+ΔU, Ua) and Sc(Uc-ΔU, Ua) are measured. In step 130, the counting mode signals can be plotted on a graph against the counting detector supply voltage. This is optional for visualization but not essential. FIG. 6 is an exemplary plot of this data. For the horizontal axis, the supply voltage Uc of the counting mode detector is plotted in volts. For the vertical axis, signal Sc in the counting mode detector is plotted in counts per second (cps). Alternatively, the signal and detector voltage can be plotted as a percentage and / or relative to the operating point. The three plotted data points are at the operating point and offset by + / -ΔU from the operating point. In this case, the operating point is 1775V and the offset points are offset by + / -10%, i.e., 1597.5V and 1952.5V. The signal values measured for the three points are listed in Table 1 below.

[0049]

Table 2

[0050] In operation 140, curve Pc is fitted to three data points. The equation of the curve for the exemplary data is shown in the graph of FIG. 6. The curve is preferably a quadratic polynomial because such an equation is the lowest order function for accurately describing three data points. However, other functions such as an exponential curve or a Fermi curve can also be used. The curve or function may be determined directly by a solution or regression. In operation 150, using the equation of the curve, the derivative of the equation Pc' is determined such that it can be calculated at any given supply voltage with gradients of Uc - 10% and Uc + 10%. In Table 1, the gradient values at each point are shown by the row labeled "Delta Signal". The row "DeltaSignal / Signal" is the gradient divided by the signal at that voltage supply setting. Thus, the value of the row "DeltaSignal / Signal" corresponds to the term Pc'(Uc0) / Pc(Uc0) of Equation 2 described above. Determining the value of this term and checking it against the tolerance of the plateau state is shown as operation 160 in FIG. 5. In operation 170, if the calculated value of the term is within the tolerance range, the operating point of the counting mode detector meets the plateau criterion and the device is ready to perform the analysis. In operation 180, if the calculated value of the term is outside the tolerance range, the operating point of the counting mode detector does not meet the plateau criterion and the device may need to be recalibrated. In such a case, it may be necessary to warn the user or automatically initiate the recalibration process. The plateau check takes about 15 seconds as compared to about 10 minutes for a full calibration according to the prior art. Thus, the plateau check is much faster and reduces the downtime of the device.

[0051] In the data of FIG. 6 and Table 1, the tolerance of Equation 2 is a change of 0.08 - 0.1% of the signal per volt at the operating point voltage, which gives a range of 0.0008 - 0.001. Based on Table 1, the value is 0.00084 and is thus within this range. In an embodiment, the value at the offset operating point may also be considered.

[0052] The calibration check is preferably performed in the background using non-sample ions such as argon ions. In this way, the check can be carried out regularly and frequently to confirm that the calibration is valid.

[0053] Figure 7 is a flowchart showing a method of performing a cross-calibration check. This method is used to check that the cross-calibration coefficient between the counting mode detector and the analog mode detector remains accurate. As described above, the counting detector is used to measure low-level ions and can have a 6 dynamic range of 10. The analog mode detector can provide an additional dynamic range of 3 to 5 digits. There is a measurement region where both detectors are operable and a cross-calibration coefficient is used to scale the measurement value of one detector to the measurement value of the other detector. The cross-calibration coefficient is determined periodically, but it is preferably necessary to check it frequently due to the aging deterioration of the detector. When one recalibration of the detector is performed, the cross-calibration coefficient is likely to need to be updated.

[0054] In FIG. 7, the first step 210 of the mutual calibration method is to measure the signals in the counting detector and the analog detector at the operating point voltages Ua and Uc. If the plateau check has already been executed, these signal values have already been measured. In step 220, the mutual calibration coefficient between the two signals is determined. This is determined simply as the ratio of the two values. Some checks on the signal quality can also be performed, such as checking that the signal level falls within the window where both detectors are effectively detecting. For example, the analog signal may be checked to exceed a first minimum threshold, and the counting signal may be checked to exceed a second minimum threshold. The second minimum threshold is higher than the first minimum threshold. The variation of the signal can also be checked to avoid large variations in the signal. The variation can be checked by calculating the relative standard deviation (RSD) and checking that it is, for example, less than 5% or 10%. If the signal does not exceed the threshold or the variation is too large, for example, a change in the analyte level or the non-analyte ion level may be required to increase the signal level. In step 230, the calculated mutual calibration coefficient is checked against the target range. In step 240, if the mutual calibration coefficient is within the target range, the device is ready for analysis. If the mutual calibration coefficient is outside the target range, in step 250, recalibration may be required and / or a warning may need to be given to the user. The target mutual calibration coefficient may be a default target value based on the design of the device. As in the case here, when non-analyte ions are used, the target value may be different, and the target value is measured and stored separately for comparison. The range may be a 5% or 2% window around that target.

[0055] The plateau check and the cross-calibration check require only a few data points that can be quickly recorded by varying the supply voltage to the detector. This can be performed when the calibration solution is the analyte within the instrument. Alternatively, and preferably, the instrument can be operated without a calibration solution. In the normal analyte measurement operation for an ICP source, a plasma is generated in an argon gas stream and the sample is introduced into the plasma through a nebulizer. The plasma can still be generated even in the absence of an analyte. Argon ions are passed through a dual-mode detector. The conversion dynode of the dual-mode detector can convert the ions into electrons for amplification in subsequent dynode stages.

[0056] The plateau check and the cross-calibration check can be applied either when an analyte is present or when no analyte is present by detecting argon ions. The checks are rapid and do not require an analyte or calibration solution, so the checks can be performed in the background without the user being aware. For example, the checks may be performed when the instrument is first turned on and ready for use, or periodically during the measurement of a sample. This allows maximizing the measurement time when an analyte is present. Alternatively, the checks may be performed while the instrument is analyzing a sample, but for the plateau check, the need to offset the counting-mode detector supply voltage requires a small amount of analysis time. On the other hand, the cross-calibration check does not require such a voltage change and can be easily performed at any point during the analysis of a sample or when the instrument is waiting with only argon ions. Thus, while the plateau check and the cross-calibration check have been described as being performed together, they may be performed at separate times or on different schedules. However, as described below, since the cross-calibration factor varies with the mass unit, the normal use of non-analyte argon ions provides a reproducible check that the cross-calibration remains valid.

[0057] As described, argon is present in ICP-MS instruments because it is used for plasma generation and stabilization and also to carry the sample into the plasma. Thus, ICP-MS always includes the abundance of argon ions. Argon can exist in several forms such as 36 Ar and 38 Ar argon ions, as well as argon 40 Ar- 40 Ar dimers and the like. Conventionally, 36 Ar and 38 Ar ions as well as 40 Ar- 40 Ar dimer presence means that it is impossible to reliably measure the amounts of other ions at these masses, i.e., 36, 38, and 80 amu.

[0058] The present invention proposes using the abundance of argon ions for detector operating point calibration, such as when the instrument is not making measurements. For example, argon gas can be flowed through the instrument to generate argon ions. The argon ions are converted to electrons, which are then detected by two detectors of a dual-mode detector. The ICP source always provides different abundances of argon ions depending on its analysis temperature and the conditions at the interface that moves the argon ions from the plasma to the mass spectrometer. In the absence of a sample, the abundance of argon can be as follows. 36 Ar: 0.334% 38 Ar: 0.063% 40 Ar: 99.6% The mass spectrometer and detection device can generally measure and distinguish these species. For example, an instrument with a typical 115 In-based sensitivity of about 400 kcps / ppb exhibits an 38 Ar ion sensitivity of 1.0 Mcps to 10 Mcps depending on the interface settings between the plasma torch and the analyzer. These count rates are easily measured by a counting mode detector. If the sensitivity of the instrument is lower than this, 36Ar ions can be measured instead, which are about 5 times more abundant. Furthermore, 40 Ar is always 40 Ar- 40 present as Ar dimers and can be used instead. Mass separation may be used and any one or more of the argon isotope ions may be detected. If some or all of these signals are out of the convenient range, they can be brought to usable levels by shifting ion source conditions such as the extraction lens voltage or the sampling depth during check / re-calibration.

[0059] The use of argon ions is preferred for the checks and calibrations described herein, but other ions may be used. All ions present in appropriate and stable abundances such as 1 to 5 Mcps can be used. The ions can be from gas additives to source gases such as helium, neon or nitrogen. However, the use of argon alone does not require a gas mixture.

[0060] As described above, the use of the always present argon ions provides a convenient check of the effectiveness of the currently used calibration. The argon ions may also be used as a recalibration. The use of argon with a plateau check and a cross-calibration check avoids the need to perform a full calibration regularly. For example, previously, if the device had not been calibrated for some time or if the device appeared to be out of calibration, the only option would have been to run a full calibration routine. This requires the user to provide a specific calibration solution to the device and thus requires user interaction to input the solution into the device. Also, there may be a need to select the correct calibration solution material and instruct the device to start the calibration routine for the user. The calibration routine of the device itself can take 10 minutes. In some cases, calibration may not have been required, such as when there is no change in the calibration factor. With the plateau check and cross-calibration check of the present invention, these checks can be performed quickly and regularly without the user or the device spending a great deal of time, and recalibration needs to be performed only when the check indicates that it is necessary. Thus, the check also provides an indication of whether calibration should be performed. Previously, for example, if the device had been calibrated very recently but the performance of the detector had drifted for some reason, measurements may have been taken with a device that was out of calibration. This can lead to incorrect measurement results.

[0061] Regarding the cross-calibration check, it should be noted that different cross-calibration factors can be applied to different ion masses. This is shown in FIG. 8. The horizontal axis shows the atomic mass of the ions entering the detection device in atomic mass units (amu). The vertical axis is the relative calibration factor between the two detectors. The triangles are the measurement data points. The line is the calculation of the cross-calibration value based on the measured values. As can be seen from the figure, the cross-calibration factor is from three digits to four digits and even up to five digits. For example, at an atomic mass of 100, the calibration factor is 100×10 3They are. These mutual calibration values are mainly determined based on ion species in one or more given samples. In the prior art, the preferred range of amu for generating mutual calibration is 100 - 150 amu. For low-mass 36 Ar and 38 Ar argon ions (encircled), it can be seen that the average detection efficiency is higher than that of heavier ions (because a lower mutual calibration coefficient is required). Therefore, calibration samples may still be needed for complete instrument calibration, but argon ions can be conveniently used for plateau and mutual calibration checks.

[0062] For mutual calibration checks, the mutual calibration coefficients for one (or more) non-analyte or multiple ions such as argon ions are measured and stored. Readjustment of the detector voltage(s), e.g., the voltage on an analog detector, is done to make the mutual calibration coefficient equal to a previously measured complete calibration value that can function as a target when setting the mutual calibration coefficient. When the detector voltage is adjusted such that the mutual calibration coefficient meets the target, the mutual calibration coefficient for non-analyte ions is effectively invariant. In that case, it can be assumed that there is no need to change the values of other ions, and the original values of other ions can continue to be used as they are. Alternatively, instead of readjusting the detector voltage, the previously measured mutual calibration coefficients may be scaled across the amu range. That is, they can be scaled according to the percentage by which the mutual calibration coefficient measured for argon ions deviates from the value it had after the last complete calibration using a calibration solution containing multiple elements across the amu range.

[0063] The inventors have discussed that the Plateau check and the cross-calibration check can indicate that recalibration is necessary. For example, failure of the Plateau check can indicate that the operating point of the counting mode detector is no longer valid. In such a case, the device may automatically initiate an on-the-fly recalibration of the operating point and perform cross-calibration based on the argon ion signal. In a further alternative, following a subsequent cross-calibration check using argon ions, if the cross-calibration or the operating point check suggests that the calibration or the operating point is no longer valid, rather than being estimated based on the response of Ar ions, assuming that the calibration data should be updated, the device may warn the user, such as by notification or alarm, enter the calibration into the device, and initiate a calibration routine.

[0064] In some cases, recalibration of the operating point may be required, and in other cases, recalibration of the cross-calibration may be required. In many cases, when the operating point is changed, the cross-calibration also needs to be changed. FIG. 9 is a flowchart showing a calibration check and a recalibration process method. FIG. 9a shows an alternative flowchart providing further details of a particular embodiment of the method, such as when the operating point is outside the range of variation of the initially tested operating point. We begin by explaining FIG. 9. The method starts by performing a cross-calibration check 310 and a plateau check 320, as described herein. These are typically done together or in any order. In step 330, the results are evaluated and an action to be taken is determined. If the results of the cross-calibration check and the plateau check are within their respective target ranges, such as 2%, 3%, or 5%, no action is required. Step 340 indicates that the cross-calibration is adjusted if only the cross-calibration is outside the target range. The process of cross-calibration is described below. Step 350 indicates that if the plateau check is outside the target range, a gain curve or operating point calibration is performed, followed by a cross-calibration adjustment. Optionally, although not shown in FIG. 9, if the cross-calibration check is outside the target range by a wide margin, such as more than 15%, here too, a gain or operating point calibration can be performed, followed by a cross-calibration adjustment. In step 360, it is determined whether it is necessary to repeat either the cross-calibration or the operation recalibration process. This is best done, for example, by performing the plateau check and the cross-calibration check already described for one complete iteration resulting from the recalibration when it is difficult to keep both the cross-calibration check and the plateau check within the target range. In such cases, the range of adjustment for calibration may need to be increased. This step is optional as the cross-calibration and the operating point may have been correctly achieved in 340 and 350. Finally, as a final verification of the recalibration, the cross-calibration check 370 and the plateau check 380 can be performed again.

[0065] As described above, FIG. 9a provides more details regarding the flowchart of FIG. 9, particularly the process 360 split into new processes 345' and 355'. Similar to FIG. 9, the method may start with performing the cross-calibration check (Xcal check) and the plateau check shown in process 310'. In relation to FIG. 9, these checks may be performed together, thus shown as a single process in FIG. 9a. The next process in FIG. 9a is to evaluate the results and determine the next process to take, as shown in process 330'. Similar to FIG. 9, the next process is determined based on whether it is determined that the operating point and / or the cross-calibration is invalid. If the operating point is valid but the cross-calibration is invalid, the cross-calibration is adjusted as shown in process 340'. As will be explained below, adjusting the cross-calibration may result in different operating points of the counter and / or the analog mode detector, so additional processes may need to be performed to set the detector to the correct operating point. These processes are shown as 345' in FIG. 9a and include the following. · Perform adjustment of the operating point (gain curve adjustment), followed by · Execute the cross-calibration check (Xcal check), if necessary · Execute the cross-calibration adjustment (Xcal Adjust), followed by · Perform further adjustment of the operating point (gain curve adjustment, second iteration). This is an iterative approach to make the operating point and the cross-calibration to more appropriate operating points. The final check of the operating point is performed at process 370', where the cross-calibration and the plateau check are executed.

[0066] FIG. 9a also shows the process to be taken when the plateau check at 310' determines that the operating point is not valid. In such a case, the method moves to process 350' and the adjustment of the operating point is performed (gain curve adjustment: first iteration). After this process, the following process 355' follows. · After performing the cross-calibration adjustment (Xcal Adjust, first iteration) · Execute the check of the operating point (plateau check), and then, if necessary, · Adjust the operating point (gain curve adjustment, second iteration), and then · Perform cross-calibration adjustment (Xcal Adjust: second iteration). Again, a final check of the operating point is performed at step 370’, where cross-calibration and plateau checks are executed.

[0067] Figure 10 is a flowchart showing a method of adjusting cross-calibration (e.g., Xcal Adjust) between a counting mode detector and an analog detector. This method can be used when cross-calibration adjustment is required, such as in step 340 of FIG. 9 or step 340’ of FIG. 9a. After pre-measuring the detector signal at the operating point in step 210, etc., the cross-calibration coefficient Xcal0 at the operating point is determined and divided by the target cross-calibration coefficient XcalT to determine two ratios. The ratio or relative difference between the two indicates how far the operating point is from the target cross-calibration and thus the amount of adjustment required. The target for a given system can be determined based on the dynamic range to be covered by the detection system. The target value is used to expand the dynamic range, for example, by 2, 4, or 6 digits. For example, a large span of cross-calibration ranges such as from 35,000 to 200,000 may be used to expand the range from approximately 1 digit to 6 digits.

[0068] In one example, when the ratio Xcal0 / XcalT is within the range of 0.5 to 2.0, the operating point voltage of the analog detector may be adjusted by only 1.25%, and the counting mode detector may be adjusted by only 2.5%. Such an adjustment process depends on the specific system to be calibrated. The direction of adjustment is to increase the voltage between the analog mode detector and the counting mode detector when the ratio is less than 1 (Xcal0 is less than XcalT), or to decrease the voltage between the analog mode detector and the counting mode detector when the ratio is less than 1 (Xcal0 is less than XcalT). For larger ratios, the adjustment range can be larger and the number of measurements required can be more. The operating point voltage is adjusted to cover the range in a series of steps at 420. The measurements are taken at each point as shown at 430. Next, as shown in step 440, a polynomial is fitted to identify the relationship between the counting mode supply voltage and the cross-calibration coefficient. For larger adjustment ranges and more measurement points, higher-order polynomials may be used. Based on the determined polynomial, the predicted and adjusted operating point voltages for the analog and counting mode detectors are determined.

[0069] Table 2 below shows some exemplary ranges of adjustment for the supply voltages of the analog detector and the counting mode detector, indicated by ΔUa and ΔUc respectively. The table also shows the number of measurement points and the degree of the polynomial that can be fitted to the data to predict the adjusted operating point voltage and the cross-calibration coefficient.

[0070]

Table 3

[0071] FIG. 11 shows a table and graph of data regarding an example of applying the method of FIG. 10 to mutual calibration adjustment when Xcal0 / XcalT>1. As can be seen from the table at the top of FIG. 11, the analog supply voltage is adjusted to increase by up to 2.5%, and the counting mode supply voltage is adjusted to decrease by up to 5%. Similar to the operating point voltage and the maximum adjustment voltage, a third measurement is made between them at a +1.25% increase in the analog voltage and a -2.5% decrease in the counting mode voltage. As seen in the table of FIG. 11, the counting mode and analog mode detector voltages are adjusted together such that the measurement points can be described as follows. (Ua,Uc), (Ua + 1.25%, Uc - 2.5%), (Ua + 2.5%, Uc - 5%).

[0072] The adjustment values in FIG. 11 correspond to the example in Table 2. Each adjustment step is based on ΔUa, ΔUc. Therefore, when Xcal0 / XcalT>1, the first adjustment value in the table of FIG. 11 is an increase of +1.25% in Ua and a decrease of 2.5% in Uc, as shown in the third column of the table in FIG. 1.

[0073] FIG. 11 also shows a graph of the data collected in the table of FIG. 11. The cross-calibration factor is plotted on the vertical axis against the analog mode detector supply voltage Ua on the horizontal axis. A quadratic polynomial or other curve is fitted to three data points. The target cross-calibration factor is 35000. The polynomial is used to calculate the value of the analog mode detector supply voltage Ua at the target cross-calibration factor. In this case, the supply voltage at the target is determined to be -2265V. Plotting the data points on the graph helps to visualize the results but is not necessarily required. The fitting of the polynomial or curve can be done without the graph. After the analog mode detector supply voltage at the target has been determined, the counting mode detector supply voltage is determined by interpolation and / or scaling between the closest points. In the example of FIG. 11, the counting mode supply voltage is determined to be 1730V. The actual cross-calibration can be checked by measuring the signal values at the new operating point voltages of the two detectors. The check is used to confirm that the cross-calibration value is within the target tolerance range.

[0074] FIG. 12 is a flowchart showing a method of adjusting the operating point voltage when the plateau check fails. In step 510, signals Sa and Sc in the counting mode detector and the analog mode detector are measured at their operating point voltages. These values may already have been determined as part of the plateau check. As step 520, the supply voltage of the counting mode detector is adjusted and the signal in the counting mode detector is measured. In step 520, it is shown that the counting mode supply voltage is stepped by + / -ΔU, + / -2ΔU. ΔU may be 10% of the counting mode detector supply voltage at the current operating point. Thus, the adjusted values are used to determine how the signal changes with the supply voltage. Step 520 indicates that signals at four adjusted voltages can be measured. Some of these, for example + / -ΔU, may already have been measured and thus need not be measured again, but in this example at least the + / -2ΔU signals need to be measured. In some embodiments, more or fewer measured values at the adjusted voltages may be used. For example, only the signal measured at + / -ΔU may be used, or more signals such as + / -ΔU, + / -2ΔU, and + / -3ΔU may be used.

[0075] FIG. 13 has a table of data collected at Uc and + / -ΔU, + / -2ΔU and + / -3ΔU. Here ΔU is 10%. The initial operating point voltage of the counting detector is set to 1625V. Signals on the counting mode detector and the analog mode detector are measured. The measured values are shown as cps (counts per second) and analog in the table respectively. The supply voltage of the counting mode detector is increased by 10, 20 and 30% and the signal is measured. The supply voltage of the analog detector does not change (during the plateau measurement). Next, the supply voltage for the counting mode detector is returned to the initial operating point voltage, the signal is re-measured, then the supply voltage of the counting mode detector is decreased by 10, 20 and 30% and the signal is measured. These measured values are shown in the table of FIG. 13.

[0076] Returning to FIG. 12, in step 530, the count mode signal is plotted on a graph against the count mode detector supply voltage. FIG. 13 includes a graph of the data in the table of that figure. As also shown in step 540, a curve such as a polynomial curve is fitted to the data. The polynomial is labeled P2c in FIG. 12. Here, a cubic polynomial is used. The table in FIG. 13 also includes the mutual calibration values calculated from the count data and the analog data. Data points with low mutual calibration coefficients are not included in the fitting of the curve to the data. As can be seen from the figure, at a count detector supply voltage reduced by 30%, the mutual calibration coefficient has a value of 39 compared to the values at 1000 seconds and 10000 seconds of other measurements. Such a low value indicates that the detector is operating in the low part of the gain curve and not near the high gain plateau region. Data points with a mutual calibration coefficient below a certain threshold can be excluded from the curve fitting. For example, the threshold for exclusion may be that the mutual calibration coefficient is less than 10% of the mutual calibration coefficient at the initial operating point or the target value.

[0077] The polynomial determined for the data points of this example is shown in the graph of FIG. 13. The derivative of the curve can be determined such that the slope of the curve can be determined at any point along the curve. Step 550 in FIG. 12 shows determining the derivative P2c' of the curve P2c and calculating the values of the curve and the derivative at the initial operating point voltage Uc and the offset voltages Uc+ / -ΔU and Uc+ / -2ΔU. In step 560, the ratio P2c'(Uc) / P2c(Uc) at the operating point is determined and evaluated to determine whether it is within the target range. The values of this ratio at the operating point and the offset are shown in the table of FIG. 13. In the exemplary data of FIG. 13, a target range between 8×10 -4 and 9×10 -4 is used. The target ratio represents the increase in the signal having a detector voltage 1V higher at (Uc-Ua), as will be further explained below. For the data of FIG. 13, this target range is between the count mode detector supply voltages of the initial operating point voltage Uc (1625V) and the offset value Uc+10% (1787.5V). By setting the nominal value within the target range, such as at the center of the target range (e.g., 8.5×10-4 ) By solving the ratio P2c’(Uc) / P2c(Uc), the value of the counting mode supply voltage that meets the target can be determined. For the data in Figure 13, the new operating point voltage is determined to be 1770V, indicated by "x" on the graph.

[0078] The 8×10 used here -4 and 9×10 -4 The target range between them is approximately equal to the condition that there is a signal decrease of >9% per 100V shift towards lower voltage from the operating point and a signal increase of <8% per 100V shift towards higher voltage from the operating point. This is approximately equivalent to the condition shown in Figure 4, which shows a curve with a 13% signal decrease per 100V shift towards lower voltage from the operating point and a 4% signal increase per 100V shift towards higher voltage from the operating point.

[0079] As shown in step 570 of Figure 12, if the target condition cannot be found within the range of the Uc and offset values used, the measurement range is extended in the appropriate direction, and additional data points, for example, Uc + 40%, Uc + 50% need to be measured.

[0080] As shown in step 350 of Figure 9 (and 355’ of Figure 9a), after the operating point is adjusted, the mutual calibration may require further adjustment. First, the mutual calibration can be checked using the mutual calibration check described in relation to Figure 7. If mutual calibration adjustment is required, the mutual calibration can be adjusted, for example, by using the method described in relation to Figures 10 and 11. In many cases, mutual calibration adjustment is not required. In a few cases, subsequent mutual calibration adjustment may significantly affect the operating point voltage of the counting mode detector, and it may be necessary to repeat the method of Figure 12. As shown in Figure 9, the recalibration can be confirmed by the final plateau and the mutual calibration check. Then, the device is ready to perform the analysis.

[0081] As described above, the calibration check and recalibration may be performed using argon ions used to flow the sample through the analyzer, and they can be performed in the background without user input.

[0082] Figure 14 is an alternative flowchart to the flowchart of Figure 9 and is a link to any user to facilitate calibration of the analyzer using a calibration solution. The method of Figure 14 can start at step 610. The first step of the method relates to setting the calibration of the device by the user using a calibration solution. The detector is calibrated at 620 using the signal from the analyte in the calibration solution. In steps 630 and 640, based on the calibration, the values obtained using non-analyte argon ions are used to determine the plateau conditions and the tolerance range of the cross-calibration check. These values are then stored for later use. After the operation of the device over a period of time, in step 650, the signal may be measured using non-analyte argon ions, and a plateau check and a cross-calibration check may be performed. In step 660, the measured value is compared with the tolerance range. If the measured value is within the range, as shown in step 690, the device is ready for analysis. In step 670, if the measured value is outside the tolerance range, a new user calibration is performed by returning to step 610 or calibration is performed using the method described herein using non-analyte argon ions. The latter can be regarded as on-the-fly calibration. The argon ion-based calibration is performed in step 680 and includes adjusting the detector supply voltage until the results of the plateau check and the cross-calibration check return to the tolerance range determined in step 640. After the results of the check return within the tolerance range, as shown in step 690, the device is ready for analysis. This procedure can be combined with continuous calibration control and analyte-based cross-calibration. This can be determined from the signals measured from unknown samples or standard samples while normal analysis tasks are being performed.

[0083] Those skilled in the art will readily understand that various modifications and changes can be made to the above-described method and apparatus. Modifications may be made without departing from the scope of the appended claims. For example, different values and ranges may be used, the order of the steps of the method may be changed, and aspects of different embodiments may be combined.

Claims

Claim 1 A method for checking the calibration of a dual-mode secondary electron multiplier (SEM) detector of a mass spectrometer using non-analyte ions, the method comprising: Setting the counting mode detector of the dual-mode SEM detector to a calibrated operating point by providing an operating point supply voltage to the counting mode detector; Using the counting mode detector to record a first counting signal related to the number of non-analyte ions incident on the SEM detector; Offsetting the operating point of the counting mode detector by adjusting the supply voltage to the counting mode detector; Using the counting mode detector to record a second counting signal at each of two or more offset operating point voltages related to the number of non-analyte ions incident on the SEM detector; Fitting a non-linear function to the values corresponding to the first and second recorded counting signals and the operating point voltage; Determining that the calibration is valid if the rate of change of the non-linear function at the calibrated operating point is within an acceptable range. Claim 2 Offsetting the operating point of the counting mode detector by adjusting the supply voltage to the counting mode detector includes offsetting the operating point to a first offset operating point at a voltage higher than the operating point voltage and offsetting the operating point to a second offset operating point at a voltage lower than the operating point voltage, Recording the second counting signal at each of the two or more offset operating point voltages includes recording an upper second counting signal at the first offset operating point voltage and recording a lower second counting signal at the second offset operating point voltage, the method according to claim 1. Claim 3 The acceptable range is an acceptable range normalized with respect to the counting signal at the calibrated operating point, the method according to claim 1 or 2. Claim 4 The normalized acceptable range is a rate of change of less than 15% of the non-linear function at the operating point, the method according to claim 3. Claim 5 The non-linear function is a quadratic polynomial, the method according to any one of claims 1 to 4. Claim 6 If the rate of change of the non-linear function at the calibrated operating point is not within the tolerance range, based on the non-linear function, estimate the supply voltage at which the rate of change of the non-linear function is within the tolerance range, and adjust the operating point to the estimated supply voltage. The method according to any one of claims 1 to 5.

7. Recording the updated first count signal in the count mode detector in a state where the operating point is changed to the estimated supply voltage, and reapplying a non-linear function to the data including the first count signal, the second recorded count signal, and the updated first count signal at the estimated supply voltage, and determining whether the rate of change of the non-linear function at the estimated supply voltage is within the tolerance range. The method according to claim 6, further comprising:

8. Estimating the supply voltage at which the count signal is within the tolerance range based on the non-linear function includes estimating the supply voltage at which the rate of change of the non-linear function is at a target value within the tolerance range. The method according to claim 6 or 7.

9. If the rate of change of the non-linear function at the calibrated operating point is not within the tolerance range, provide a warning to the user requesting the user to perform recalibration of the count mode detector. The method according to any one of claims 1 to 8.

10. If it is determined that the calibration is not valid, perform recalibration of the count mode detector. The method according to any one of claims 1 to 9.

11. The recalibration is Offsetting the operating point of the count mode detector by adjusting the supply voltage to the count mode detector to one or more second offset voltages, Using the count mode detector to record a third count signal at each of the one or more second offset operating point voltages related to the incidence of non-sample ions in the SEM detector, Fitting a second non-linear function to the first, second, and third recorded count signals and the values corresponding to the operating point voltages, Based on the second non-linear function, estimating the supply voltage at which the rate of change of the second non-linear function is within a second tolerance range, and adjusting the operating point to the estimated supply voltage. The method according to claim 10, comprising:

12. The second non-linear function is a cubic polynomial. The method according to claim 11.

13. The method according to claim 11 or 12, wherein the second allowable range is that the change rate of the non-linear function at the operating point is less than 5%, less than 9%, less than 10%, or less than 15%.

14. recording an analog signal in the analog mode detector of the dual mode secondary ion detector; calculating a mutual calibration coefficient between the analog mode detector and the counting mode detector based on the first counting signal and the analog signal at the operating points of the counting mode detector and the analog mode detector; further comprising checking whether the mutual calibration coefficient is within a window or a target calibration coefficient, the method according to any one of claims 1 to 13.

15. The method according to claim 14, wherein when it is determined that the mutual calibration is not valid, a mutual calibration correction between the counting mode detector and the analog mode detector is performed.

16. The mutual calibration correction includes: recording a first analog mode signal related to the number of non-specimen ions incident on the SEM detector using the analog mode detector at the operating point supply voltage; recording a first mutual calibration counting mode signal related to the number of non-specimen ions incident on the SEM detector using the counting mode detector; offsetting the operating points of the analog mode detector and the counting mode detector by adjusting the supply voltages to the analog mode detector and the counting mode detector; recording a second analog mode signal and a second mutual calibration counting mode signal related to the number of non-specimen ions using the analog mode detector and the counting mode detector at the adjusted supply voltages; repeating the steps of offsetting and recording a further second analog mode signal and a further second mutual calibration counting mode signal; determining a mutual calibration coefficient for the first analog mode signal, the second analog mode signal, the further second analog mode signals, and the counting mode signals; adapting a third non-linear function to the values corresponding to the first, second, and further second analog mode signals, and the operating point voltage of the analog detector; estimating the supply voltage of the analog detector at which the mutual calibration coefficient is within an allowable range or meets a target based on the third non-linear function. Based on whether the mutual calibration coefficient is within an acceptable range or the estimated analog detector supply voltage meets a target, estimating a counting mode detector supply voltage for the acceptable range or target; Adjusting the operating point voltages of the analog mode detector and the counting mode detector to the estimated supply voltage, the method according to claim 15.

17. The method according to any one of claims 1 to 16, wherein the non-analyte ions are argon ions, noble gas ions or nitrogen ions.

18. The method according to any one of claims 1 to 17, wherein the steps according to any one of claims 1 to 17 are performed using non-analyte ions without a calibration solution.

19. The method according to any one of claims 1 to 18, wherein the steps according to any one of claims 1 to 18 are performed before analyzing a sample and / or in the background without warning the user.

20. The method according to claim 19, wherein the method is performed at regular intervals in the background without warning the user.

21. A method for checking the calibration of a dual-mode secondary electron multiplier (SEM) detector of a mass spectrometer, the method comprising: Obtaining a first count signal from a counting mode detector at an operating point voltage, the first count signal being related to the amount of non-analyte ions incident on the SEM detector; Obtaining a second count signal related to the non-analyte ions at two or more offset operating point voltages of the counting mode detector; Fitting a non-linear function to the first and second count signals and the values corresponding to the operating point voltage; Determining that the calibration is valid when the rate of change of the non-linear curve at the calibrated operating point is within an acceptable range.

22. A computer-readable medium storing instructions that, when executed by a processor, cause the processor to perform the method according to claim 21.

23. A mass spectrometer comprising a dual-mode secondary electron multiplier (SEM) detector configured to perform the method according to any one of claims 1 to 21.

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