Mass spectrometer and method of calibrating mass spectrometer

Abstract

The present disclosure describes a method of checking the calibration of a dual mode secondary electron multiplier (SEM) detector of a mass spectrometer using non-analyte ions, the method includes: using a count mode detector of the dual mode SEM detector at an operating point voltage to record a first count signal related to a number of non-analyte ions incident to the SEM detector; offsetting the operating point of the count mode detector and recording a second count signal related to the number of non-analyte ions incident to the SEM detector at respective two or more offset operating point voltages; fitting a non-linear function to the recorded first and second count signals and values corresponding to these operating point voltages; and 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. A mass spectrometer configured to perform the method is also described.

Description

Technical Field

[0001] The present invention relates to secondary electron multiplier (SEM) detectors, such as for detecting ions emerging from a mass analyzer of a mass spectrometer. Specifically, the present invention relates to the calibration of such detectors and to checking the existing calibration of the detectors. Background Art

[0002] Mass spectrometry is a series of techniques for identifying and quantifying substances in materials. Elemental mass spectrometry is a branch of mass spectrometry in which it is necessary to determine the types and amounts of chemical elements present in a sample. For precise measurement, a wide dynamic range is required, or at least beneficial.

[0003] A secondary electron multiplier (SEM) detector is a detector having a surface coated with a secondary emission material. When electrons strike the secondary emission 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 be increased many times, such as increased by a million times. Such detectors may be referred to as electron multiplier detectors. One type of mass spectrometry using such detectors is inductively coupled mass spectrometry (ICP-MS).

[0004] To achieve a wide dynamic range, an SEM detector can be a dual-mode detector having two operating modes, namely a counting or pulse mode and an analog mode. The counting mode can provide a dynamic range of 10 6 and the analog mode can provide an additional three to four orders of magnitude of dynamic range. Generally, these two operating modes have a certain range of overlap to allow calibration of one mode relative to the other. Some systems have an additional electrometer 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] Figure 1More details of the structure of a dual-mode SEM ion detector are schematically shown. The ion detection device includes a series of dynodes (shown as D1 - 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 referred to as a conversion dynode because it converts the incoming ions into electrons. The dynodes are at a suitable potential which is negative and increases (becomes closer to ground) as one moves from the first dynode D1 to the last dynode D8. Although the drawings show eight dynodes, other numbers of dynodes may be used. The one or more electrons generated by the first / conversion dynode are accelerated by the potential towards the next dynode. At each subsequent dynode, the impact of the electrons at the dynode generates one or more secondary electrons and they are again attracted to the next dynode. This results in a cascade of increasing numbers of electrons. For example, for a single electron arriving at D1, there may be millions of electrons incident on the detector T1. The detector T1 can collect the 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 referred to as a pulse or count signal S c . The amplification provided by the series of dynodes is large. If the number of ions entering the detection device is relatively high, the number of electrons arriving at the detector T1 may be greater than the maximum detectable signal that the dynamic range of the detector can accommodate. As Figure 1 shown, a second output signal, referred to as an analog signal S A , can be output from midway along the series of dynodes. For example, in Figure 1 , the analog signal is derived from the fifth dynode out of eight dynodes. Generally speaking, the dynode providing the analog signal will be midway along the series of dynodes, e.g., at the middle dynode of the series. Since the amplification of the number of electrons at the fifth dynode is not as large as at the eighth dynode, for a larger number of input ions, the analog signal will continue to provide an output signal, thus increasing the dynamic range relative to the single pulse / count signal.

[0006] For example, for inductively coupled plasma mass spectrometry (ICP-MS), the detection device should be able to operate over a dynamic range of nine orders of magnitude and preferably greater. This enables the detection device to detect both major and minor components of a sample.

[0007] As mentioned in the previous paragraph, the two detection modes can be calibrated relative to each other within the range of operation of the two detectors. Once calibrated, the system should provide reliable quantitative output for days, weeks, or even months depending on the intensity used. However, due to the aging effect of the dynode surface material, a problem with the dual-mode SEM detector is the drift of its amplification factor.

[0008] US 5,463,219 and US11,469,091 B1 describe a dual-mode secondary electron multiplier detector used in a mass spectrometer. GB 2421841 A 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 rapid method for checking whether the existing calibration of a counting mode detector remains accurate. The method also provides a rapid method for checking the cross-calibration between a counting mode detector and an analog mode detector, as well as a method for recalibration. These methods can be executed by a mass spectrometer instrument in the background or during idle time without user input. The method can use argon ions derived from argon gas as a carrier gas, which is used to generate sample ions and cause the sample ions to flow through the spectrometer. When no sample is present, argon gas can flow through the spectrometer, and thus calibration checks and calibrations can be performed without the need for a calibration sample or solution. Argon gas and / or other non-analyte gases can be used.

[0010] The present invention provides a method for using non-analyte ions to check the calibration of a dual-mode secondary electron multiplier (SEM) detector of a mass spectrometer, the method comprising: setting the counting mode detector to a calibrated operating point by providing an operating point supply voltage to the counting mode detector of the SEM detector; using the counting mode detector to record a first count signal based on the number or amount 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 second count signals related to the number or amount of non-analyte ions incident on the SEM detector at one, two, or more corresponding offset supply voltages; fitting a non-linear curve or function to the recorded first count signal and second count signals and the values corresponding to the supply voltages of the counting mode detector; 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" refers to ions that are not analytes, i.e., they are not part of the sample being analyzed. Non-analyte ions can include ions used to cause the sample to flow through the analyzer, such as carrier gas ions or carrier ions. Non-analyte ions can include argon ions, which can be derived from a carrier gas and / or a plasma gas. Non-analyte ions can additionally or alternatively include calibrant ions generated from a calibration solution. The term "non-analyte ions" includes majority ions. Generally, majority ions include carrier gas ions but do not include calibrant ions.

[0011] The counting signal referred to herein may relate to the number of counts detected by a counting mode detector over a time period such as one second, or the average number of counts over such a time period. The counts may be actual counts of incident electrons, detection of charged particles, or accumulation of voltage. The use of curve fitting allows for a quick determination of whether the operating point has shifted and needs adjustment, and indicates the amount and direction of the adjustment that may be required. Specifically, curve fitting generally allows determination of the amount and direction of adjustment without the need for an additional offset operating point voltage.

[0012] Shifting the operating point of a counting mode detector by adjusting the supply voltage may include: shifting the operating point to a first offset operating point at a voltage higher than the operating point voltage; and shifting the operating point to a second offset operating point at a voltage lower than the operating point voltage; and wherein recording a second counting signal at two or more respective offset operating point voltages includes: recording a higher second counting signal at the first offset operating point voltage and a lower second counting signal at the second offset operating point voltage. Alternatively, the second counting signal may be measured at one offset operating point or more than one offset operating point. In an embodiment, the offset operating points may all be at voltages higher or lower than the operating point voltage. The so-called operating point voltage refers to the voltage at which the detector operates for analysis, such as a voltage determined by an earlier calibration or preset by other means.

[0013] The acceptable range may be an acceptable range normalized with respect to the counting signal at the calibrated operating point.

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

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

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

[0017] The method may further include: recording an updated first counting signal at the counting mode detector in the case where the operating point is changed to the estimated supply voltage; refitting the non-linear curve or function to data including the first counting signal, the second counting signal, and the updated first counting signal at the estimated supply voltage; and determining whether the rate of change of the non-linear curve or function is within the acceptable range at the estimated supply voltage.

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

[0019] The method may further include: 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, providing a reminder to the user to request the user to perform recalibration of the count mode detector.

[0020] The method may include: when determining that the calibration is invalid, performing recalibration of the count mode detector.

[0021] Recalibration of the count mode detector may 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 the corresponding one or more second offset operating point voltages based on the number or amount of non-analyte ions incident on the SEM detector; fitting a second non-linear curve or function to the recorded first count signal, second count signal, and third count signal and the values corresponding to the supply voltage of the count mode detector; and estimating the supply voltage at which the rate of change of the second non-linear curve or function will be 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 third-order polynomial.

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

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

[0025] The method may include: in the case of determining that the cross-calibration is invalid, performing correction of the measured cross-calibration between the count mode detector and the analog mode detector.

[0026] The cross-calibration correction may include: using an analog mode detector at an analog mode detector operating point supply voltage to record a first analog mode signal related to the number or amount of non-analyte ions incident on the SEM detector; using a counting mode detector at a counting mode detector operating point supply voltage to record a first cross-calibration counting mode signal of the number or amount of non-analyte ions incident on the SEM 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; using the analog mode detector and the counting mode detector at the adjusted supply voltages to record a second analog mode signal and a second cross-calibration counting mode signal related to the number or amount of non-analyte ions incident on the SEM detector; repeating the steps of offsetting and recording additional second analog mode signals and additional second cross-calibration counting mode signals; determining cross-calibration factors for the first analog mode signal, the second analog mode signal, the additional second analog mode signals, and the counting mode signals; fitting a third non-linear curve or function to the first analog mode signal, the second analog mode signal, the additional second analog mode signals, and the values corresponding to the operating point voltages of the analog mode detector; estimating an analog detector supply voltage for which the cross-calibration factor is within an acceptable range or meets a target based on the third non-linear curve or function; estimating a counting mode detector supply voltage for the acceptable range or target based on the estimated analog detector supply voltage for which the cross-calibration factor is within the acceptable range or meets the target; and adjusting the operating point voltages of the analog mode detector and the counting mode detector to the estimated supply voltages.

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

[0028] The methods described herein may be performed using non-analyte ions without a calibration solution.

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

[0030] The method may be performed in the background at fixed intervals without alerting the user.

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

[0032] The present invention provides a method for calibrating 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 counting signal, the second counting signal, and the values corresponding to the supply voltage of the counting - mode detector; 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.

[0033] A computer - readable medium stores instructions that, when executed by a processor, cause the processor to perform the foregoing method.

[0034] A mass spectrometer includes a dual - mode secondary electron multiplier (SEM) detector configured to perform any of the methods described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Embodiments of the present invention and aspects of the prior art will now be described with reference to the drawings, wherein:

[0036] Figure 1 is a schematic diagram of a dual - mode SEM - type detector;

[0037] Figure 2 is a schematic diagram of detector supply voltage versus the normalized count rate of the counting - mode detector;

[0038] Figure 3is a graph of the normalized count rate of the total detector supply voltage versus the count detector, showing the change in the operating point due to detector aging;

[0039] Figure 4 is a graph of the normalized count rate of the total detector supply voltage versus the count detector, showing the platform standard for a given operating point;

[0040] Figure 5 is a flowchart of a method for checking the operating point of a count detector using a platform standard according to an embodiment of the present invention;

[0041] Figure 6 is a graph showing the measured values from a count mode detector versus the count mode detector supply voltage, for checking whether the operating point meets the platform standard;

[0042] Figure 7 is a flowchart of a method for performing a cross - calibration check between a count mode detector and an analog mode detector;

[0043] Figure 8 is an example graph showing the cross - calibration between an analog detector and a count mode detector across an atomic mass unit range. The data circled in black are from non - analyte ions 36Ar and 38Ar;

[0044] Figure 9 is a flowchart of a method for checking and, if necessary, recalibrating a count mode detector and an analog mode detector;

[0045] Figure 9a is a flowchart of a method for recalibrating a count mode detector and an analog mode detector according to an embodiment of the present invention;

[0046] Figure 10 is a flowchart of a method for adjusting the cross - calibration between a count mode detector and an analog detector;

[0047] Figure 11 includes Figure 10 a table and graph of example data of a cross - calibration adjustment method;

[0048] Figure 12 is a flowchart of a method for adjusting the operating point voltage or gain curve of a count mode detector;

[0049] Figure 13 includes Figure 12 a table and graph of example data for adjusting the operating point voltage or gain curve of a count mode detector according to the method of; and

[0050] Figure 14It is a flowchart of a method for checking and calibrating an analyzer, including user-prompted calibration with a calibration solution. Detailed implementation mode

[0051] As previously described, Figure 1 is a schematic diagram of a dual-mode detector, which may include, for example, multiple dynodes. The voltage on the first / conversion dynode will be negative and relatively high. The voltage on the subsequent dynodes will increase such that they remain negative but with a decreasing magnitude. The voltage on the subsequent dynodes in this series can be positive and gradually become positive towards the end of the series of dynodes. The voltage difference between consecutive dynodes can be the same. In some embodiments, the voltage difference between the first two dynodes can be higher than the voltage difference between other dynodes. In some embodiments, for the subsequent dynodes, the voltage difference can increase sequentially. The following table provides example voltages for a dual-mode detection device with eight dynodes as Figure 1 shown. The table also includes the voltage that is positive at detector T1. Thus, detector T1 is sometimes considered the anode of the detection device. The values given in the following table are example voltages for a positive ion dual-mode detector without a separate conversion dynode. Ions will be converted into secondary electrons with 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 form.

[0052]

[0053] Increasing the magnitude of the voltage on the dynodes and detector T1 will tend to increase the amplification of the number of electrons, such that the gain at the analog and pulse count signals increases. However, when the voltage is maintained at a higher magnitude, the dynodes are more likely to age faster. This may be due to the aging effect on the surface material of the dynodes.

[0054] Figure 2 is a schematic diagram 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 at the analog detector and the pulse count or counting mode detector. For more common positive ion detection, the voltage at the detector entrance is negative to attract positive ions into the detector. Thus, the voltage at 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:

[0055] |-Ua| + Uc

[0056] Where Uc is the voltage at the counting detector and Ua is the voltage at the analog detector. Since Ua is usually negative, its magnitude is taken here to write the sum. This sum value is a measure of how strongly electrons are accelerated from the analog detector to the surface of the counting detector dynode and is thus a measure of the amount of secondary electrons that can be generated. Return to Figure 2 , the ordinate is a measure of the count rate of the pulse / counting detector at the corresponding detector voltage after normalizing the count rate of the pulse / counting detector at the operating point voltages for the analog and counting detectors. By definition, in the schematic curve, the count rate at the operating point WP voltage is one. At lower voltages, the count rate decreases at an increasing rate, while at higher voltages, the count rate increases but very slowly. This is due to the fact that at a well-calibrated WP, there are only very few electron pulses remaining outside the detection threshold of the detection system. A well-calibrated WP is characterized by detecting >90% of all electron pulses generated by ions incident on the detector.

[0057] As mentioned before, aging of the dynode can cause the amplification factor to change. Figure 3 Shows how aging of the dual-mode SEM detection device causes the gain curve to shift and the operating point to shift. As the detector ages, the shape of the gain curve remains essentially the same, but the operating point and the specific gain require an increasing voltage. Similar to Figure 2 , Figure 3 , the abscissa shows the total detector voltage |-Ua|+Uc (written as Uc-Ua in the figure) applied to the dynode of the connected detector, where Uc is the voltage at the counting dynode and -Ua is the voltage at the analog detector. The ordinate shows the normalized count rate, i.e., the count rate in the total voltage range normalized for the signal at the operating point when Uc-Ua is at the operating point (measured at the pulse / counting detector T1). Figure 3 Shows four measured gain curves. The measured data points for each curve in the different curves are represented as squares, diamonds, circles, and triangles respectively. The curve with data points represented as squares has the lowest aging level and the lowest total voltage. For this curve, the operating point is approximately 3950V. The curves with data points represented by diamonds, circles, and triangles represent increasing aging respectively. These operating points are approximately 4050V, 4150V, and 4210V respectively.

[0058] To determine the operating point, the total detector supply voltage is changed and the corresponding change in the count at the counting detector is analyzed. For a dual-mode detector having a supply voltage Ua for the analog detector and a supply voltage Uc for the counting detector, respectively, the operating point is defined by a platform criterion. This criterion checks the slope of the gain curve at the operating point. Ideally, the operating point will be at the total voltage where the gain is maximum. However, as schematically shown in Figure 2 and also visible in Figure 3 , although the gain becomes almost flat at higher supply voltages, it still continues to rise slightly. Thus, a simple algorithm to maximize the gain can lead to pushing the detector supply voltage to a high level, resulting in detector aging. Therefore, preferably, the operating point voltage is set to the point where the steep increase in gain has slowed down for increasing supply voltages.

[0059] The platform criterion is used to check whether the gain slope at the operating point is towards a plateau of the curve approaching the maximum gain. This criterion is characterized by checking that the operating point is approaching the maximum by requiring that the signal loss is within an acceptable range when the detector supply voltage is decreased. In other words, the platform criterion checks whether the operating point is set close to the plateau. If the operating point is far from the plateau and descends along a steeper part of the slope of the decreasing signal, a given change in the supply voltage away from the operating point will result in a large drop in the signal. Due to the detector type and signal variation, the signal variation is normalized according to the signal at the operating point. As mentioned above, the operating point voltages for the counting detector and the analog detector can be Uc and -Ua, respectively. The change in the operating point voltage is given by ΔU. The platform criterion can be defined by the following formula:

[0060]

[0061] Figure 4Shows the signal variation for a series of operating points. The nominal operating point voltage (Uc + |-Ua|) is set to approximately 3950V, which is identified as 100% signal in the attached figure. For a ±100V change in the operating point voltage supplied to the detector, i.e., 3850V and 4050V, the change in 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. According to the above formula, this change is written as 0.129 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. Thus, at an operating point voltage of 3950V, the detector operates to meet the plateau criterion. Under this criterion, the response flattens significantly such that even at a supply voltage of 4250V, in the context of the overall graph, the count rate hardly increases above 105%. Therefore, when the voltage is set to the WP value, more than 90% of the pulses are detected.

[0062] Alternatively, since most of the variation in 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 and Ua can be kept fixed. Thus, the plateau criterion can be written solely based on the variation of the signal with 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:

[0063]

[0064] where Pc'(Uc0) is the gradient of the function at the operating point voltage and Pc(Uc0) is the value of the function at the operating point voltage.

[0065] Figure 5 Is a flowchart showing a method for checking the operating point of a counting detector using the plateau criterion according to an embodiment of the present invention. The method includes: setting the counting mode detector and the analog mode detector to their operating point voltages; and measuring the signal Sc at the counting mode detector and the signal Sa at the analog mode detector at step 110. Although the signal Sa at the analog mode detector is not necessary for the plateau check, measuring it at this point is useful because it may be needed later for cross-calibration checks between the two detectors. At step 120, the supply voltage to the counting mode detector is adjusted by ±ΔU, and the corresponding counting mode signals Sc(Uc + ΔU, Ua) and Sc(Uc - ΔU, Ua) are measured. At step 130, the counting mode signal can be plotted on a graph with respect to the counting detector supply voltage. This is optional for visualization but not necessary. Figure 6This is an example graph of the data. The supply voltage Uc of the counting mode detector is plotted on the horizontal axis in volts. The signal Sc at the counting mode detector is plotted relative to the vertical axis 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 data points plotted are at the operating point and offset from the operating point by ±ΔU. In this case, the operating point is 1775 V and the offset points are offset by ±10%, i.e., 1597.5 V and 1952.5 V. The measured signal values for the three points are listed in Table 1 below.

[0066]

[0067] Table 1

[0068] At step 140, the curve Pc is fitted to these three data points. The formula for the curve of the example data is shown in the Figure 6 graph. This curve is preferably a second-order polynomial since such a formula is the lowest-order function for accurately describing three data points. However, other functions such as exponential or Fermi curves can be used. The curve or function can be determined directly by a solution method or by a regression method. Using the formula for the curve, at step 150, the derivative Pc' of the formula is determined such that the gradient can be calculated at any given supply voltage, such as for Uc - 10% and Uc + 10%. In Table 1, the values of the gradient at the corresponding points are indicated by the row labeled "Delta signal". The row "Delta signal / signal" is the gradient divided by the signal at that voltage supply setting. Thus, the values in the "Delta signal / signal" row correspond to the term |Pc'(Uc0) / Pc(Uc0)| in Equation 2 discussed previously. As shown in step 160 of Figure 5 , the value of this term is determined and checked against the acceptable range for the platform condition. At step 170, if the calculated value of this term is within the acceptable range, the operating point of the counting mode detector meets the platform criteria and the instrument is ready to perform the analysis. At step 180, if the calculated value of this term is outside the acceptable range, the operating point of the counting mode detector does not meet the platform criteria and the instrument may need to be recalibrated. In this case, it may be necessary to alert the user or automatically start the recalibration process. Compared to a full calibration of approximately 10 minutes according to the prior art, the platform check takes approximately 15 seconds. Thus, the platform check is much faster, reducing the downtime of the instrument.

[0069] In Figure 6 and the data in Table 1, the acceptable range for Equation 2 is a signal change of 0.08% - 0.1% per volt at the operating point voltage, which gives a range of 0.0008 to 0.001. Based on Table 1, the value is 0.00084 and is thus within this range. In an embodiment, the values at the offset operating points can also be considered.

[0070] Preferably, non-analyte ions such as argon ions are used to perform calibration checks in the background. In this way, checks can be performed regularly and frequently to confirm whether the calibration is valid.

[0071] Figure 7 is a flowchart showing a method of performing a cross-calibration check. This method is used to check whether the cross-calibration factor between the counting mode detector and the analog mode detector remains accurate. As mentioned before, the counting detector is used to measure low levels of ions and can have a dynamic range of 10 6 . The analog mode detector can provide an additional dynamic range of 3 to 5 orders of magnitude. There is a measurement region where both detectors can operate, and the cross-calibration factor is used to scale the measured values on one detector to the measured values on the other detector. The cross-calibration factor is determined periodically, but preferably needs to be checked frequently due to the aging of the detectors. If recalibration of one of the detectors is performed, it may be necessary to update the cross-calibration factor.

[0072] In Figure 7 , the first step 210 of the cross-calibration method is to measure the signals at the counting detector and the analog detector at the operating point voltages Ua and Uc. If a plateau check has been performed, these signal values should already have been measured. At step 220, the cross-calibration factor between the two signals is determined. This is simply determined as the ratio of the two values. Some checks on the signal quality can also be performed, such as by checking that the signal levels fall within the window where both detectors can effectively detect. For example, the analog signal can be checked to see if it exceeds a first minimum threshold, and the counting signal can be checked to see if it exceeds a second minimum threshold. The second minimum threshold should be higher than the first minimum threshold. The variation of the signal can also be checked to avoid large fluctuations in the signal. This variation can be checked by calculating the relative standard deviation (RSD) and checking if it is less than, for example, 5% or 10%. If the signal does not exceed the threshold or there is too much variation, it may be necessary to change the analyte level or the non-analyte ion level, for example to increase the signal level. At step 230, the calculated cross-calibration factor is checked against the target range. If the cross-calibration factor is within the target range, at step 240, the instrument is ready for analysis. If the cross-calibration factor is outside the target range, at step 250, recalibration may be required and / or the user may need to be alerted. The target cross-calibration factor can be a default target value based on the design of the instrument. If non-analyte ions are used, as is the case here, the target value can be different, and the target value will be measured and saved separately for comparison. The range can be a 5% or 2% window around the target.

[0073] Platform checks and cross-calibration checks require only a small number of data points, which can be quickly recorded by varying the supply voltage to the detector. This can be performed when the calibration solution is the analyte in the instrument. Alternatively and preferably, the instrument can operate without a calibration solution. In normal analyte measurement operation for an ICP source, a plasma is generated in an argon gas stream, where the sample is introduced into the plasma through a nebulizer. A plasma can still be generated in the absence of an analyte. Argon ions are transmitted to a dual-mode detector. The conversion dynode of the dual-mode detector can convert the ions to electrons for amplification in subsequent dynode stages.

[0074] Platform checks and cross-calibration checks can be applied by detecting argon ions whether an analyte is present or not. The checks are rapid and, since no analyte or calibration solution is required, can be performed in the background without the user being aware. For example, the checks can be performed when the instrument is first turned on and ready for use, or periodically between measurements of samples. This allows the measurement time when an analyte is present to be maximized. Alternatively, the checks can be performed while the instrument is analyzing a sample, but for platform checks, the supply voltage of the counting-mode detector needs to be offset, which will take a small amount of analysis time. On the other hand, cross-calibration checks do not require such voltage changes and can be easily performed at any point during sample analysis or when the instrument is on standby with only argon ions. Thus, although platform checks and cross-calibration checks have been described as being performed together, they can be performed at separate times or on different schedules. However, as will be described below, the cross-calibration factor varies with mass unit, so the periodic use of non-analyte argon ions provides a reproducible check that the cross-calibration remains valid.

[0075] As discussed, argon is present in an ICP-MS instrument because it is used for plasma generation and stabilization and also for carrying the sample to the plasma. Thus, an ICP-MS will always include the abundance of argon ions. Argon can exist in multiple forms, such as 36 Ar and 38 Ar argon ions, and argon 40 Ar- 40 Ar dimer. Typically, 36 Ar and 38 Ar ions and 40 Ar- 40 Ar dimer presence means that the amounts of other ions at these masses, i.e., 36 amu, 38 amu, and 80 amu, cannot be reliably measured.

[0076] The present invention proposes using argon ion abundance for calibrating the operating point of a detector, such as when the instrument is not making measurements. For example, an argon gas flow can be passed through the instrument to generate argon ions. The argon ions are converted into electrons, and then the electrons are detected by two detectors of a dual-mode detector. The ICP source will always provide argon ions with different abundances, depending on its analysis temperature and the conditions in the interface that transfers the argon ions from the plasma to the mass analyzer. In the absence of an analyte, the abundances of argon can be:

[0077] 36 Ar: 0.334%

[0078] 38 Ar: 0.063%

[0079] 40 Ar: 99.6%

[0080] The mass analyzer and the detection device will generally be able to measure and distinguish these species. For example, an instrument with a typical 115 In-based sensitivity of about 400 kcps per ppb will show an 38 Ar ion sensitivity between 1.0 Mcps and 10 Mcps, depending on the interface settings between the plasma torch and the analyzer. These count rates can be easily measured by a counting mode detector. If the instrument is not so sensitive, instead, 36 Ar ions with an abundance about five times higher can be measured. In addition, 40 Ar is always present in the form of 40 Ar- 40 Ar dimers, and it can also be used instead. Mass separation can be used and any one or more of the argon isotope ions can be detected. If some or all of these signals are outside a convenient range, they can be brought to an available level by changing the extraction lens voltage or ion source conditions (such as the sampling depth during inspection / re-calibration).

[0081] Although argon ions are preferably used for the inspection and calibration described herein, other ions can also be used. All ions present in a suitable and stable abundance (such as 1 - 5 Mcps) can be used. These ions can come from gases added to the source gas, such as helium, neon, or nitrogen. However, using argon gas alone does not require a gas mixture.

[0082] As discussed, the use of persistent argon ions provides a convenient check on the validity of the calibrations currently in use. Argon ions can also be used for recalibration. The use of argon gas for platform checks and cross-calibration checks obviates the need to perform full calibrations on a regular basis. For example, previously if the instrument had not been calibrated for some time or the instrument appeared to be out of calibration range, the only option would be to perform a full calibration routine. This would require the user to supply the instrument with specific calibration solutions and thus would require user interaction to input the solutions into the instrument. The correct calibration solution material might also need to be selected and the user would need to instruct the instrument to start the calibration routine. The calibration routine of the instrument itself might take 10 minutes. In some cases, calibration might not be needed, such as when the calibration factors have not changed. With the platform checks and cross-calibration checks of the present invention, these checks can be performed quickly and regularly without taking up a significant amount of user or instrument time and recalibration is only needed when the checks indicate that recalibration is necessary. Thus, the checks also provide an indication of whether calibration should be performed. Previously, measurements might have been made on an instrument that was out of calibration range, for example, if the instrument had recently been calibrated but the performance of the detector had been changed for some reason. This could result in incorrect measurement results.

[0083] Regarding cross-calibration checks, it should be noted that different cross-calibration factors can be applied to different ion masses. This is shown in Figure 8 . The abscissa shows the atomic mass of the ions entering the detection device in atomic mass units (amu). The ordinate is the relative calibration factor between two detectors. The triangles are the measured data points. The line is the calculation of the cross-calibration values based on the measured values. As can be seen, the cross-calibration factors are three to four or even five orders of magnitude. For example, at an atomic mass of 100, the calibration factor is 100×10 3 . These cross-calibration values are mainly determined based on the ion species in one or more given samples. In the prior art, the preferred range of amu for generating cross-calibration is 100 - 150 amu. It can be seen that for the low mass 36 Ar and 38 Ar argon ions (circled), their average detection efficiency is higher than that of the heavier ions (because a lower cross-calibration factor is required). Thus, calibration samples might still be needed for a full instrument calibration, but argon ions can be conveniently used for platform and cross-calibration checks.

[0084] For cross - calibration checks, the cross - calibration factors for one (or more) non - analytes or major ions, such as argon ions, are measured and stored. The detector voltage (e.g., the voltage on an analog detector) is readjusted so that the cross - calibration factor equals a previously measured full - calibration value, which can serve as the target for setting the cross - calibration factor. When the detector voltage has been adjusted such that the cross - calibration factor meets the target, the cross - calibration factor for the non - analyte ions remains effectively unchanged. Then, it can be assumed that the values for other ions do not need to be changed, and the original values for the other ions can continue to be used without change. Alternatively, instead of readjusting the detector voltage, the previously measured cross - calibration factors can be scaled across the amu range. That is, they can be scaled based on the percentage by which the measured cross - calibration factor for argon ions deviates from the value it had after the last full - calibration using a calibration solution containing multiple elements across the amu range.

[0085] It has been discussed that platform and cross - calibration checks can indicate the need for recalibration. For example, a failure of the platform check can indicate that the operating point of the counting - mode detector is no longer valid. In this case, the instrument can automatically initiate an immediate recalibration of the operating point and perform a cross - calibration based on the argon ion signal. In an additional alternative, after a subsequent cross - calibration check using argon ions, if the cross - calibration or operating - point check indicates that the calibration or operating point is no longer valid, the instrument can alert the user, such as by notification or alarm, to enter the calibration into the instrument and initiate a calibration routine, assuming that the preferred approach is that the calibration data should be updated rather than estimating based on the response of the Ar ions.

[0086] In some cases, a recalibration of the operating point may be required, while in other cases, a recalibration of the cross - calibration may be needed. Generally, if the operating point changes, the cross - calibration will also need to change. Figure 9 is a flowchart showing the method of calibration checks and recalibration procedures. Figure 9a An alternative flowchart showing more details of a specific implementation of the method is presented, such as when the operating point is outside the range of variation of the operating point of the initial test. First, starting from Figure 9 is described. The method starts with performing a cross - calibration check 310 and a platform check 320 as described herein. These are typically performed together or in any order. At step 330, the results are evaluated to determine the action to be taken. If the results of the cross - calibration check and the platform check are within their respective target ranges, such as 2%, 3%, or 5%, no action is required. Step 340 indicates that if only the cross - calibration is outside the target range, the cross - calibration is adjusted. The process of cross - calibration will be described below. Step 350 indicates that if the platform check is outside the target range, a gain - curve or operating - point calibration is performed, followed by a cross - calibration adjustment. Optionally, and at Figure 9If not shown in the figure, if the cross-calibration check exceeds the target range by a wide margin, such as by 15% or more, gain or operating point calibration can also be performed here, and then cross-calibration adjustment is carried out. At step 360, it is determined whether any cross-calibration or re-calibration steps need to be repeated. For example, if it is difficult to bring both the cross-calibration and the platform check into the target range, this is preferably done by performing the platform and cross-calibration checks described above for a complete re-calibration iteration. In this case, it may be necessary to increase the adjustment range of the calibration. This step is optional because the cross-calibration and operating point may have been correctly achieved at 340 and 350. Finally, the cross-calibration check 370 and the platform check 380 can be performed again as the final verification of the re-calibration.

[0087] As described above, Figure 9a more details of the Figure 9 flowchart are provided, especially more details about step 360, which is split into new steps 345' and 355'. Similar to Figure 9 this, the method can start by performing a cross-calibration check (Xcal check) and a platform check, which is indicated at step 310'. It has been pointed out regarding Figure 9 that these checks can be performed together and are thus indicated in Figure 9a a single step. Figure 9a The next step in Figure 9 is to evaluate the results and decide on the next steps to take, as indicated at step 330'. Similar to Figure 9a this, the next steps are determined based on whether the operating point and / or cross-calibration are determined to be invalid. If the operating point is valid but the cross-calibration is invalid, the cross-calibration is adjusted as indicated at step 340'. As discussed below, since adjusting the cross-calibration may result in different operating points for the counter and / or the analog mode detector, additional steps may be required to set the detector to the correct operating point. These steps are indicated at 345' in

[0088] · Perform an adjustment of the operating point (gain curve adjustment), and then

[0089] · Perform a cross-calibration check (Xcal check), and as needed

[0090] · Perform a cross-calibration adjustment (Xcal adjustment), and then

[0091] · Perform a further adjustment of the operating point (gain curve adjustment, second iteration).

[0092] This is an iterative method to bring the operating point and cross-calibration to a more appropriate operating point. A final check of the operating point is performed at step 370', where the cross-calibration and platform checks are carried out.

[0093] Figure 9a Also shown are the steps to be taken if the platform check at 310' determines that the operating point is invalid. In this case, the method moves to step 350' and performs an adjustment of the operating point (gain curve adjustment: first iteration). This step is followed by the steps set forth at 355':

[0094] · Perform cross-calibration adjustment (Xcal adjustment, first iteration), then

[0095] · Perform a check of the operating point (platform check), and then as needed

[0096] · Perform an adjustment of the operating point (gain curve adjustment: second iteration), then

[0097] · Perform cross-calibration adjustment (Xcal adjustment: second iteration).

[0098] A final check of the operating point is performed again at step 370', where cross-calibration and platform check are performed.

[0099] Figure 10 is a flowchart of a method for showing cross-calibration (e.g., Xcal adjustment) between an adjustment count mode detector and an analog detector. When cross-calibration adjustment is required, such as at Figure 9 step 340 or Figure 9a step 340' as described, this method can be used. After the signal of the detector at the operating point has been measured previously, such as at step 210, the cross-calibration factor Xcal0 at the operating point is determined and divided by the target cross-calibration factor XcalT to determine the ratio between the two. The ratio or relative difference between the two indicates how far the operating point is from the target cross-calibration and thus indicates 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 orders of magnitude. A large span of cross-calibration range can be used, such as from 35,000 to 200,000, for example, to expand this range by about one order of magnitude up to 6 orders of magnitude.

[0100] In one example, if the ratio Xcal0 / XcalT is in the range between 0.5 and 2.0, the operating point voltage of the analog detector can be adjusted by 1.25% and the counting mode detector can be adjusted by 2.5%. Such adjustment steps will depend on the particular system to be calibrated. If the ratio is less than one (Xcal0 is less than XcalT), the direction of adjustment will be such that the voltage between the analog mode detector and the counting mode detector is increased, or if the ratio is greater than one (Xcal0 is greater than XcalT), the voltage between the analog mode detector and the counting mode detector will be decreased. For larger ratios, the adjustment range can be larger and the number of measurements required can be greater. At 420, the operating point voltage is adjusted in a series of steps to cover the range. Measurements are made at the corresponding points, as indicated at 430. Then a polynomial is fitted to specify the relationship between the counting mode supply voltage and the cross-calibration factor, as set forth in step 440. For larger adjustment ranges and more measurement points, higher order polynomials can be used. Based on the determined polynomial, the predicted adjusted operating point voltages for the analog mode detector and the counting mode detector are determined.

[0101] Table 2 below shows some example adjustment ranges for the supply voltages for the analog detector and the counting mode detector, denoted by ΔUa and ΔUc respectively. The table also shows the number of measurement points and the order of the polynomial that can be fitted to the data to predict the adjusted operating point voltage and the cross-calibration factor.

[0102]

[0103] Table 2

[0104] Figure 11 shows data related to an example of applying the Figure 10 method when Xcal0 / XcalT > 1 to cross-calibration adjustment, and a graph. As can be seen from the Figure 11 table at the top, the analog supply voltage is adjusted to increase by a maximum of 2.5%, and the counting mode supply voltage is adjusted to decrease by a maximum of 5%. As with the operating point voltage and the maximum adjustment voltage, a third measurement is made between these voltages when the analog voltage increases by +1.25% and the counting mode voltage decreases by -2.5%. As can be seen from the Figure 11 table, the counting mode and analog mode detector voltages are adjusted together such that the measurement points can be described as:

[0105] (Ua,Uc),(Ua + 1.25%,Uc - 2.5%),(Ua + 2.5%,Uc - 5%)

[0106] Figure 11The adjustment values therein correspond to the examples in Table 2. Each adjustment step is accomplished by ΔUa and ΔUc. Thus, for Xcal0 / XcalT > 1, Figure 11 the first adjustment value in the table is that Ua increases by +1.25% and Uc decreases by 2.5%, as Figure 1 shown in the third column of the table in

[0107] Figure 11 Also shown is a graph of the data collected in the table in Figure 11 The analog mode detector supply voltage Ua is plotted on the horizontal axis and the cross - calibration factor is plotted on the vertical axis. A second - order polynomial or other curve is fitted to three data points. The target cross - calibration factor is 35,000. This 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 this is not necessary. The polynomial or curve fitting can be done without the need for a graph. After the analog mode detector supply voltage at the target has been determined, the counting mode detector supply voltage is determined by interpolating and / or scaling between the nearest points. In the example in Figure 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. This check is used to confirm that the cross - calibration value is within an acceptable range of the target.

[0108] Figure 12 is a flowchart showing a method of adjusting the operating point voltage such as if the platform check fails. At step 510, the signals Sa and Sc at the counting mode detector and the analog mode detector are measured at their operating point voltages. These values may have been determined as part of the platform check. At step 520, the supply voltage of the counting mode detector is adjusted and the signal at the counting mode detector is measured. At step 520, the counting mode supply voltage is shown to step in ±ΔU, ±2ΔU. ΔU can be 10% of the counting mode detector supply voltage at the current operating point. Thus, the adjustment values are used to determine how the signal varies with the supply voltage. Step 520 shows that the signals at four adjustment voltages can be measured. Some of these, such as ±ΔU may have been measured and thus do not need to be measured again, but at least the signals at ±2ΔU will need to be measured in this example. In some embodiments, more or fewer measurements at the adjustment voltages can be used. For example, only the signals measured at ±ΔU can be used, or more signals such as those measured at ±ΔU, ±2ΔU and ±3ΔU can be used.

[0109] Figure 13A table with 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 indicated in the table by cps (counts per second) and analog values respectively. The supply voltage of the counting mode detector is increased by 10%, 20%, and 30% and the signals are measured. The supply voltage of the analog detector remains unchanged (during the plateau measurement). Then, the supply voltage of the counting mode detector returns to the initial operating point voltage and the signals are re-measured, and then the supply voltage of the counting mode detector is decreased by 10%, 20%, and 30% and the signals are measured. Figure 13 The measured values are shown in the table of

[0110] Return to Figure 12 , at step 530, the counting mode signal is plotted against the counting mode detector supply voltage on a graph. Figure 13 A graph of the data in the table including this figure. Also, as indicated at step 540, a curve such as a polynomial curve is fitted to the data. The polynomial is labeled as P2c in Figure 12 . A third-order polynomial is used here. Figure 13 The table of also includes values for cross-calibration calculated from the counting and analog data. Data points with low cross-calibration factors are not included in the curve fitting to the data. As can be seen, at a 30% reduction in the counting detector supply voltage, the cross-calibration factor has a value of 39 compared to the values in other measurements of 1000s and 10000s. Such a low value indicates that the detector is operating on the low part of the gain curve and not near the high-gain plateau region. Data points with cross-calibration factors below a specific threshold can be excluded from the curve fitting. For example, the threshold for exclusion can be that the cross-calibration factor is less than 10% of the cross-calibration factor or the target value at the initial operating point.

[0111] The polynomial determined for the data points of this example is shown on the graph of Figure 13 . The derivative of the curve can be determined such that the gradient of the curve can be determined at any point along the curve. Figure 12 Step 550 of indicates 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. At step 560, the ratio P2c'(Uc) / P2c(Uc) at the operating point is determined and evaluated to determine if it is within the target range. As shown in the table of Figure 13 , the values of this ratio at the operating point and the offset are indicated. For the example data of Figure 13 , using 8×10 -4 versus 9×10 -4The target range therebetween. The target ratio represents the increase in the signal having a detector voltage 1V higher at (Uc - Ua), as will be described further below. For Figure 13 the data, this target range is between the counting mode detector supply voltage at the initial operating point voltage Uc (1625V) and the offset value Uc + 10% (1787.5V). By setting a nominal value, such as in the middle of the target range (e.g., 8.5×10 -4 ), the ratio P2c'(Uc) / P2c(Uc) can be solved to determine the value of the counting mode supply voltage that meets the target. For Figure 13 the data, the new operating point voltage is determined to be 1770V, which is indicated by an "x" on the graph.

[0112] The target range used here between 8×10 -4 and 9×10 -4 is approximately equal to the condition that there is a signal drop >9% for every 100V offset from the operating point to a lower voltage, and there is a signal increase <8% for every 100V offset from the operating point to a higher voltage. This is approximately equivalent to Figure 4 the condition shown in, which shows a curve with a 13% signal drop for every 100V offset from the operating point to a lower voltage and a 4% signal increase for every 100V offset from the operating point to a higher voltage.

[0113] As Figure 12 indicated at step 570 in, if the target condition cannot be found within the range of Uc and offset values used, then it will be necessary to expand the measurement range in the appropriate direction and measure additional data points, such as Uc + 40%, Uc + 50%.

[0114] As Figure 9 indicated at step 350 in (and Figure 9a at 355' in), after the operating point has been adjusted, it may be necessary to further adjust the cross-calibration. The cross-calibration can first be checked using the cross-calibration check described regarding Figure 7 . If the cross-calibration needs to be adjusted, then it can be adjusted, for example, by using the methods described regarding Figure 10 and Figure 11 . In many cases, no cross-calibration adjustment will be required. In a few cases, subsequent cross-calibration adjustment may significantly affect the operating point voltage of the counting mode detector, and it may be necessary to repeat the Figure 12 method. As Figure 9 indicated, the recalibration can be confirmed through the final platform and cross-calibration check. Then the instrument is ready to perform the analysis.

[0115] As discussed above, the calibration check and recalibration can be performed using argon ions that flow the sample through the analyzer, and they can be performed in the background without user input.

[0116] Figure 14 Yes Figure 9 is an alternative flowchart of the flowchart of, and is linked to an optional user prompted calibration of the analyzer with a calibration solution. Figure 14 The method of can start at step 610. The first step of the method involves the user setting the calibration of the device using a calibration solution. At 620, the detector is calibrated with the signal from the analyte in the calibration solution. At steps 630 and 640, based on this calibration, the values obtained using non-analyte argon ions are used to determine the acceptable ranges for the platform conditions and cross-calibration checks. These values are then stored for later use. After the instrument has been operating for some time, at step 650, non-analyte argon ions can be used to measure the signal, and platform checks and cross-calibration checks can be performed. At step 660, the measured value is compared with the acceptable range. If the measured value is within the range, the instrument is ready for analysis, as indicated at step 690. At step 670, if the measured value is outside the acceptable range, a new user calibration is performed by returning to step 610, or calibration is performed using non-analyte argon ions using the method set forth herein. The latter can be considered an in-situ calibration. The calibration based on argon ions is performed at step 680 and includes: adjusting the detector supply voltage until the results of the platform check and cross-calibration check return to the acceptable range determined at step 640. After the results of the checks return to the acceptable range, the instrument is ready for analysis, as indicated at step 690. This process can be combined with continuous calibration control and analyte-based cross-calibration. This can be determined based on the measurement signals from unknown samples or standard samples when performing regular analysis tasks.

[0117] Those skilled in the art will readily understand that various modifications and variations can be made to the above methods and devices. Modifications can be made without departing from the scope of the appended claims. For example, different values and ranges can be used, the order of the steps of the method can be changed, and aspects of different embodiments can be combined.

Claims

1. A method of checking the calibration of a dual-mode secondary electron multiplier (SEM) detector of a mass spectrometer using non-analyte ions, the method comprising: setting a 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; recording, using the counting mode detector, a first count signal related to a number of non-analyte ions incident on the SEM detector; shifting the operating point of the counting mode detector by adjusting the supply voltage to the counting mode detector; recording, using the counting mode detector, a second count signal related to the number of non-analyte ions incident on the SEM detector at respective two or more offset operating point voltages; fitting a nonlinear function to the recorded first count signal and the second count signal and a value corresponding to the operating point voltage; as well as In the event that the rate of change of the nonlinear function at the calibrated operating point is within an acceptable range, it is determined that the calibration is valid.

2. The method of claim 1 , wherein shifting the operating point of the counting mode detector by adjusting the supply voltage to the counting mode detector comprises: shifting the operating point to a first shifted operating point at a voltage higher than the operating point voltage; and shifting the operating point to a second shifted operating point at a voltage lower than the operating point voltage; and Wherein recording the second count signal at the corresponding two or more offset operating point voltages includes: recording a higher second count signal at a first offset operating point voltage and recording a lower second count signal at a second offset operating point voltage.

3. The method according to claim 1 or claim 2, wherein the acceptable range is an acceptable range normalized with respect to the count signal at the calibrated operating point. 4 . The method of claim 3 , wherein the normalized acceptable range is a rate of change of the nonlinear function at the operating point of less than 15%.

5. A method according to any preceding claim, wherein the non-linear function is a second order polynomial.

6. A method according to any preceding claim, wherein, when the rate of change of the nonlinear function at the calibrated operating point is not within the acceptable range, estimating the supply voltage at which the rate of change of the nonlinear function will be within the acceptable range based on the nonlinear function; and adjusting the operating point to the estimated supply voltage.

7. The method according to claim 6, further comprising: recording an updated first count signal at the count mode detector when the operating point changes to the estimated supply voltage; refitting a nonlinear function to data including the first count signal, the recorded second count signal, and the updated first count signal at the estimated supply voltage; and determining whether the rate of change of the nonlinear function at the estimated supply voltage is within the acceptable range.

8. The method of claim 6 or claim 7, wherein estimating the supply voltage at which the count signal will be within the acceptable range based on the non-linear function comprises: The supply voltage at which the rate of change of the nonlinear function is at a target value within the acceptable range is estimated.

9. A method according to any preceding claim, wherein if the rate of change of the non-linear function at the calibrated operating point is not within the acceptable range, a reminder is provided to a user requesting the user to perform a recalibration of the counting mode detector.

10. A method according to any preceding claim, wherein in the event that the calibration is determined to be invalid, a recalibration of the counting mode detector is performed.

11. The method of claim 10, wherein the recalibration comprises: shifting the operating point of the counting mode detector by adjusting the supply voltage to the counting mode detector to one or more second offset voltages; recording, using the counting mode detector, a third count signal associated with the incident of non-analyte ions at the SEM detector at corresponding one or more second offset operating point voltages; fitting a second nonlinear function to the recorded first count signal, second count signal, and third count signal and a value corresponding to the operating point voltage; as well as The supply voltage at which the rate of change of the second nonlinear function will be within a second acceptable range is estimated based on the second nonlinear function, and the operating point is adjusted to the estimated supply voltage. The method of claim 11 , wherein the second nonlinear function is a third-order polynomial.

13. The method of claim 11 or claim 12, wherein the second acceptable range is a rate of change of the nonlinear function at the operating point of less than 5%, less than 9%, less than 10% or less than 15%.

14. A method according to any preceding claim, further comprising: recording an analog signal at an analog mode detector of the dual-mode secondary ion detector; calculating a cross calibration factor between the analog mode detector and the counting mode detector based on the first count signal and the analog signal at operating points of the counting mode detector and the analog mode detector; as well as Check whether the cross calibration factor is within the window or is the target calibration factor.

15. The method of claim 14, wherein in the event that the cross calibration is determined to be invalid, performing a cross calibration correction between the counting mode detector and the analog mode detector.

16. The method of claim 15, wherein the cross-calibration correction comprises: recording, using the analog mode detector at the operating point supply voltage, a first analog mode signal related to a quantity of non-analyte ions incident on the SEM detector; recording, using the counting mode detector, a first cross-calibration counting mode signal related to a number of non-analyte ions incident on the SEM detector; shifting 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 cross-calibration counting mode signal related to the number of non-analyte ions using the analog mode detector and the counting mode detector at the adjusted supply voltage; repeating the steps of shifting and recording additional second analog mode signals and additional second cross calibration count mode signals; determining a cross calibration factor for the first analog mode signal, the second analog mode signal and the further second analog mode signal and the counting mode signal; as well as fitting a third nonlinear function to the first analog mode signal, the second analog mode signal and the further second analog mode signal and to a value corresponding to the operating point voltage of the analog detector; as well as estimating an analog detector supply voltage at which the cross calibration factor is within an acceptable range or meets a target based on the third nonlinear function; estimating a counting mode detector supply voltage for an acceptable range or target based on the estimated analog detector supply voltage for which the cross calibration factor is within an acceptable range or meets a target; as well as The operating point voltages of the analog mode detector and the counting mode detector are adjusted to the estimated supply voltage.

17. A method according to any preceding claim, wherein the non-analyte ions are argon ions, noble gas ions or nitrogen ions.

18. A method according to any preceding claim, wherein the steps of any preceding claim are performed in the absence of a calibration solution using non-analyte ions.

19. A method according to any preceding claim, wherein the steps of any preceding claim are performed under the following conditions: Before the sample is analyzed; and / or Executes in the background without notifying the user.

20. The method of claim 19, wherein the method is performed at regular intervals in the background without alerting a user.

21. A method of 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 an amount of non-analyte ions incident on the SEM detector; obtaining a second count signal associated with the non-analyte ion at two or more offset operating point voltages of the counting mode detector; fitting a nonlinear function to the first count signal and the second count signal and a value corresponding to the operating point voltage; as well as In the case where the rate of change of the nonlinear curve at the calibrated operating point is within an acceptable range, it is determined that the calibration is valid.

22. A computer readable medium storing instructions which, when executed by a processor, cause the processor to perform the method of 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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