Amplifier amplitude digital control for mass spectrometers

Abstract

Control of signal amplitudes applied to the rods of a quadrupole is described herein. In one aspect, a mass spectrometer includes an amplifier circuit that applies radio frequency (RF) signals to the rods of the quadrupole. A controller circuit can determine that an actual amplitude of the RF signals is different from an expected amplitude, and in response, identify current and past environmental and performance parameters to adjust the amplitude.

Description

Technical Field

[0001] This disclosure relates to mass spectrometry analysis, and more specifically to controlling the amplitude of radio frequency (RF) signals applied to the mass analyzer, ion guide, and ion trap of a mass spectrometer. Background Technology

[0002] Mass spectrometry is an analytical technique used to measure the mass-to-charge ratio (m / z) of ions. Typically, a sample is introduced into the ion source of a mass spectrometer for ionization. The resulting ions are then transported, confined, and separated by various components of the mass spectrometer. Radio frequency (RF) signals and direct current (DC) signals are typically applied to the electrodes of the components to generate electric fields used to manipulate ions for transport, confinement, and separation.

[0003] For example, some mass spectrometers use a quadrupole mass filter, a set of four parallel bars as a mass analyzer to separate ions based on their m / z. A first oscillating RF signal is applied to two of the four bars of the quadrupole, while another oscillating RF signal, 180° out of phase with the first RF signal, is applied to the other two bars. Based on the ion's m / z, the amplitudes of the RF and analytical DC signals, and the frequency of the RF signals, the application of the RF signals, together with the analytical DC signals applied to the bar pairs with opposite polarities, generates an oscillating electric field that causes the selected ions to propagate through the quadrupole.

[0004] RF amplifier circuits can generate RF signals with amplitudes of several kilovolts to produce oscillating electric fields to resolve larger masses. The accuracy and precision of the RF signal allow for the proper generation of these oscillating electric fields. Analog feedback circuitry systems can sample the RF signal and use feedback loops to adjust the amplifier, ensuring that the actual amplitude is the same as or close to the expected amplitude. Unfortunately, analog feedback circuitry systems can include several components, thus increasing cost. Furthermore, analog feedback circuitry systems have relatively slow response times. Therefore, the actual amplitude of the RF signal cannot be quickly adjusted to the expected amplitude, thus degrading the performance of the mass spectrometer. Summary of the Invention

[0005] One innovative aspect of the subject matter described in this disclosure includes a mass spectrometer comprising: a quadrupole mass analyzer; an amplifier circuit configured to generate a first RF signal based on an amplifier radio frequency (RF) input signal; a circuit configured to receive the first RF signal and generate a second RF signal applied to a pair of poles of the quadrupole mass analyzer; an analog-to-digital converter (ADC) configured to receive the second RF signal and generate a digitized second RF signal; and a controller circuit configured to: receive the digitized second RF signal; determine an actual amplitude of the second RF signal based on the digitized second RF signal; determine that the actual amplitude of the second RF signal differs from an expected amplitude of the second RF signal; determine current environmental and performance parameters of the mass spectrometer; determine an amplitude correction applied to the amplifier RF input signal based on the actual amplitude, the current environmental and performance parameters, and historical environmental and performance parameters; and adjust the amplifier RF input signal according to the amplitude correction so that the actual amplitude of the second RF signal is adjusted to the expected amplitude.

[0006] In some implementations, the current environmental parameters include the temperature of the components of the mass spectrometer.

[0007] In some implementations, the component is one or more of the following: an inductor of a resonant circuit, or one or both of the pairs of bars of the quadrupole mass analyzer.

[0008] In some implementations, the current performance parameters include the operating mode of the quadrupole mass analyzer.

[0009] In some implementations, the controller circuitry is further configured to: determine the DC voltage applied to one or both bars of the pair of bars of the quadrupole mass analyzer; determine that the DC voltage is different from a desired DC voltage; and adjust the DC voltage to be closer to the desired DC voltage.

[0010] In some implementations, the DC voltage is adjusted to be closer to the expected DC voltage based on the historical environment and performance parameters.

[0011] In some implementations, the controller circuit is further configured to: determine characteristics instructing how the resonant circuit should perform; and adjust the second RF signal based on the determination of the characteristics instructing how the resonant circuit should perform.

[0012] In some implementations, determining the characteristics that indicate how the resonant circuit performs includes: providing a pulse waveform to the amplifier circuit; and determining the resonant frequency of the resonant circuit based on the frequency of the second RF signal generated in response to the pulse waveform.

[0013] In some implementations, the controller circuitry includes specific digital logic that performs the amplitude correction.

[0014] Another innovative aspect of the subject matter described in this disclosure includes an apparatus comprising: an amplifier circuit configured to drive electrodes of a mass spectrometer component based on an amplifier radio frequency (RF) input signal; and a controller circuit configured to provide the amplifier RF input signal in response to determining that the actual amplitude of the RF signal differs from an expected amplitude, and providing the amplifier RF input signal based on one or both of: (i) current and past environmental parameters of the mass spectrometer, or (ii) current and past performance parameters.

[0015] In some implementations, the current environmental parameters include the temperature of the components of the mass spectrometer.

[0016] In some implementations, the component is one or more of the following: a multipolar assembly, an ion director, an ion trap, a stacked ring ion director, or an ion funnel.

[0017] In some implementations, the inductor is configured to provide the RF signal to drive the electrodes of the component, and also to provide the amplifier RF input signal based on the temperature of the inductor.

[0018] In some implementations, the past environmental parameters include the temperature of the components of the mass spectrometer.

[0019] In some implementations, the component is one or more of the following: a rod of a multi-polar assembly, an ion guide, an ion trap, a stacked ring ion guide, or an ion funnel.

[0020] In some implementations, the past performance parameters include how the mass spectrometer performs during operating modes.

[0021] In some implementations, the component is a quadrupole mass filter.

[0022] Another innovative aspect of the subject matter described in this disclosure includes a method comprising: generating an amplifier RF input signal to drive an amplifier circuit configured to apply the RF signal to a multipole quality analyzer; determining, by a controller circuit, that the actual amplitude of the RF signal differs from the expected amplitude of the RF signal; identifying, by the controller circuit, one or both of the following: (i) current and past environmental parameters of the multipole quality analyzer, or (ii) current and past performance parameters of the multipole quality analyzer; and adjusting, by the controller circuit, the amplifier RF input signal, taking into account one or both of the following: (i) current and past environmental parameters of the multipole quality analyzer, or (ii) current and past performance parameters of the multipole quality analyzer.

[0023] In some implementations, the current and past performance parameters include one or more of the following: the scan rate of the mass spectrometer, or the operating mode of the mass spectrometer.

[0024] In some implementations, the current and past environmental parameters include the temperature of the components of the mass spectrometer containing the multipole mass analyzer.

[0025] In some implementations, the component is one or more of the following: an inductor configured to apply the RF signal to the resonant circuit of the quadrupole mass analyzer, a rod of the multipole mass analyzer, an ion director, an ion trap, a stacked ring ion director, or an ion funnel. Attached Figure Description

[0026] Figure 1 An example of digital control over the amplitude of the RF signal generated by the amplifier is shown.

[0027] Figure 2 An example of a block diagram for digital control of the amplitude of an RF signal is shown.

[0028] Figure 3 An example of digital control of a direct current (DC) voltage is shown.

[0029] Figure 4 An example of a block diagram for the digital control of a DC voltage is shown.

[0030] Figure 5 An example of determining the characteristics of a resonant circuit is shown.

[0031] Figure 6 An example of a block diagram for determining the characteristics of a resonant circuit is shown.

[0032] Figure 7 An example of a mass spectrometer is shown that digitally controls the amplitude of an RF signal generated by an amplifier.

[0033] Figure 8 An example of a block diagram is shown for digitally controlling the amplitude of an RF signal by identifying harmonics.

[0034] Figure 9 An example of a block diagram showing digital control of an RF signal by identifying phase differences is shown.

[0035] Figure 10 Examples of electronic devices that can be used to implement some of these examples are shown.

[0036] Figure 11 This illustrates another example of digital control over the amplitude of the RF signal generated by the amplifier. Detailed Implementation

[0037] Some of the materials described in this disclosure include circuitry and techniques for controlling the amplitude of signals generated by amplifier circuitry for mass spectrometry analysis. In one example, the mass spectrometer includes an ion source for ionizing the analyte. The resulting ions are then fed to a quadrupole mass analyzer for mass analysis. The quadrupole mass analyzer includes four parallel conductive (e.g., metallic) bars. In addition to a direct current (DC) resolution voltage, radio frequency (RF) signals are applied to two of the bars, said RF signals being 180° out of phase with the RF signals applied to the other two bars of the quadrupole. The RF signals applied to the bars oscillate within the interpeak amplitude, generating an oscillating electric field for manipulating the ions based on their mass-to-charge ratio (m / z).

[0038] The RF signal is generated by an RF amplifier circuit and can be measured in thousands of volts (V) during oscillation (e.g., peak-to-peak amplitudes up to 8000V). The RF signal is applied to the rod via an LC circuit or resonant circuit, which is modeled as including a series-coupled inductor and capacitor to act as a resonator to store energy, amplify the voltage, and oscillate at a specific frequency.

[0039] As mentioned earlier, the accuracy and precision of the RF signal amplitude are crucial for allowing the proper generation of an oscillating electric field to manipulate ions. That is, the amplitude of the RF signal must be carefully applied to ensure that ions at a specific m / z are manipulated through the quadrupole. The amplitude of the RF signal is adjusted when different ions at different m / z are selected for analysis. Unfortunately, the difference between the actual amplitude and the expected amplitude of the RF signal generated by the amplifier circuit can occur due to environmental factors (e.g., temperature variations), component degradation over time, or other factors.

[0040] As described later in this disclosure, digital control of the amplitude of the RF signal applied to the quadrupole is performed by the amplifier circuitry. For example, a controller circuit (consisting of an arrangement of connected electronic components collectively performing the desired function or operation) having digital logic functionality (e.g., implemented by a field-programmable gate array (FPGA), microprocessor, etc.) receives a digital representation of the RF signal via an analog-to-digital converter (ADC) and determines the actual characteristics of the RF signal, including its amplitude. The controller circuitry can then compare the actual amplitude with the expected amplitude, and if they differ, access a memory storing information indicating how the amplifier circuitry should be driven to provide an RF signal with the expected amplitude. This results in the actual amplitude of the RF signal being adjusted to be closer to or equal to the expected amplitude. Additionally, the controller circuitry can implement digital signal processing (DSP) to identify the amplitude of the fundamental frequency of the RF signal while ignoring harmonics, thereby allowing for more precise driving of the amplifier to generate the RF signal.

[0041] Also described later in this disclosure, the controller circuitry can determine one or both of the environmental or performance characteristics, including the temperature of components of the mass spectrometer (e.g., the temperature of the inductor coil of the resonant circuit or quadrupole, the temperature of the digital-to-analog converter) or the operating mode, and how to execute that operating mode (e.g., how to execute a scan mode or how to execute a selected monitoring mode). Scan modes may include, but are not limited to, full scan, product ion scan, precursor scan, and neutral loss scan. Selective monitoring modes may include, but are not limited to, selective ion monitoring (SIM) and selective reaction monitoring (SRM). Operating modes may include scan rate, start m / z, end m / z, and time spent in that mode. Operating modes may also include previously executed or upcoming operating modes. One or both of the current environmental and performance characteristics, as well as one or both of the historical environmental and performance characteristics, can also be used to more precisely drive the amplifier to generate the RF signal.

[0042] Also described later in this disclosure, the phase difference between the actual RF signal and the RF amplifier input signal used to drive the amplifier can be determined. This phase difference is often a result of harmonics causing the actual RF signal to differ from the expected RF signal. This can be caused by a drift in the resonant frequency of the resonant circuit during temperature variations affecting the capacitor or inductor of the resonant circuit. The RF amplifier input signal can be adjusted to compensate for the phase difference, resulting in the actual RF signal being closer to or the same as the expected RF signal (e.g., at the resonant frequency).

[0043] In addition to controlling the amplitude, the above techniques can also be used to control the frequency or phase of the actual RF signal.

[0044] By controlling the amplitude (or frequency or phase) of the RF signal via controller circuitry, the appropriate amplitude can be achieved much faster than when using analog circuitry to determine how to adjust the amplitude. This results in increased throughput for the mass spectrometer due to a reduction in the "dead time" between scans. Furthermore, fewer components are used, leading to cost savings compared to analog circuitry. Additionally, the controller circuitry can record information related to the RF signal, environment, and performance, as well as access a history of past information to make more informed decisions about amplitude adjustment. The controller circuitry can also allow the mass spectrometer to self-calibrate to levels impossible using analog techniques.

[0045] More in detail, Figure 1 An example of digital control over the amplitude of the RF signal generated by the amplifier is shown. Figure 2 It shows the Figure 1 An example of a block diagram for the digital control of the amplitude of an RF signal. In Figure 2 In this process, the RF signal applied to the quadrupole is digitized (205). For example, in Figure 1 In this configuration, RF input 105 is the signal that drives the components of RF amplifier 110. In response, the RF amplifier generates RF signal 115, which is a higher power signal than RF input 105. RF signal 115 is provided to the terminals of inductors 130a and 130b (which are out of phase with respect to the other, such that inductors 130a and 130b provide out-of-phase signals to their respective poles) to generate RF signals 155 and 160, respectively. Inductor 130a is coupled to poles 125a and 125b of quadrupole 120, and inductor 130b is coupled to poles 125c and 125d of quadrupole 120. The resonant circuit (LC circuit) is implemented by the inductance of the inductor and the capacitance of the rod, and thus the voltage of the RF signal 115 is amplified to provide out-of-phase RF signals 155 and 160, for example, with an inter-peak amplitude of up to 8000V, to the rods 125a and 125b and rods 125c and 125d of the quadrupole 120, to generate an appropriate electric field to manipulate the ions according to their m / z. Figure 1 The examples provided are merely one type of circuit that can be implemented. For instance, RF amplifier 115 can drive a primary coil, which in turn drives secondary coils similar to inductors 130a and 130b to generate RF signals 155 and 160. In another example, a resonant circuit is not required. Instead, a non-resonant transformer or other circuitry can be implemented.

[0046] like Figure 1As shown, a digital representation of the RF signal 160 is provided to the controller circuit 135 via an analog-to-digital converter (ADC) 140. That is, the ADC 140 receives the analog-format RF signal 160, samples it, and generates a digital representation of the RF signal 160 provided to the controller circuit 135. Figure 1 In this context, it is described that the ADC 140 receives the RF signal after the inductor. Although in Figure 1 Only RF signal 160 is digitized, but RF signal 155 (as mentioned earlier, which is out of phase with RF signal 160) can also be tapped and digitized in a similar manner.

[0047] Although depicted as a separate circuit, the functionality of ADC 140 can be implemented within controller circuitry 135. In one example, ADC 140 could be a 20MHz ADC that samples a 1MHz waveform to sample a sufficient number of points in the digital representation of the RF signal 160. By digitizing the RF signal 160 using ADC 140, new information can be determined and used to drive the RF amplifier 110 more precisely, which would otherwise be impossible in analog control typically used with mass spectrometers.

[0048] Back Figure 2 Then, the actual amplitude of the digitized RF signal is determined (210). For example, in Figure 1 In this circuit, controller circuit 135 receives digital representations and determines the amplitude of RF signal 160 by identifying the highest peak or amplitude in the data representing points of the waveform or by using other techniques as discussed later herein.

[0049] Next, in Figure 2 In this context, the actual magnitude is compared with the expected magnitude (215). For example, in... Figure 1 In this configuration, controller circuit 135 compares the actual amplitude of RF signal 160 with the expected amplitude at which RF signal 160 should be located at quadrupole 120 to generate an accurate and precise oscillating electric field that positions ions at a specific m / z within a stable region. The actual amplitude may differ from the expected amplitude due to changes in environmental conditions (e.g., component temperature, noise interfering with RF signals 160 or 155, etc.), degradation of mass spectrometer components, etc. If controller circuit 135 determines that the actual amplitude differs from the expected amplitude, it can adjust the actual amplitude to be the same as or closer to the expected amplitude by driving RF amplifier circuit 110 differently via RF input 105 (e.g., by changing the amplitude of RF input 105).

[0050] In some implementations, a variable capacitor can be included in the resonant circuit and tuned (e.g., its capacitance adjusted) to modify the amplitude. Using a variable capacitor allows adjustment of the resonant frequency, but amplitude adjustment becomes more difficult (though possible). Alternatively, a variable inductor can be implemented in the resonant circuit, and its inductance can be adjusted to modify the amplitude. By ensuring that the RF signal 160 is at or near the desired amplitude, the oscillating electric field generated by the quadrupole 120 allows for more precise selection of ions passing through specific m / z for mass analysis.

[0051] exist Figure 2 If the actual amplitude differs from the expected amplitude, the controller circuit 135 further determines the current performance and / or environmental characteristics (220), and then uses the current and historical performance and / or environmental characteristics to determine amplitude correction (225). For example, the controller circuit 135 may include, or be accessible, a memory storing information about how the quadrupole 120 (or other components of the mass spectrometer) operated in the past and the environmental conditions of the quadrupole 120 in the past. Under these historical conditions, the amplifier 110 may have been driven differently (i.e., the amplitude of the RF input 105 may have been different) to provide the expected amplitude on the RF signal 160. Therefore, by comparing the current performance and environmental characteristics with historical performance and environmental characteristics and the actual and expected amplitudes, all the information stored in the memory can be used, for example via a lookup table (LUT), to determine the amplitude correction. The amplitude correction indicates how much the amplitude of the RF input 105 should be adjusted so that the RF signal 160 is closer to the expected amplitude. The controller circuit 135 can then adjust the amplitude of the RF input 105 according to the amplitude correction recommended in the LUT (e.g., increasing or decreasing the amplitude of the RF input 105 by amplitude correction), so that the actual amplitude of the RF signal 160 is changed to be closer to or even equal to the expected amplitude. In the previous example, performance and environmental characteristics were used. However, the controller circuit 135 can use one or both of the performance and environmental characteristics. For example, current performance characteristics and historical performance characteristics can be used instead of environmental characteristics (current or historical) to determine the amplitude correction. In another example, current environmental characteristics and historical environmental characteristics can be used instead of performance characteristics to determine the amplitude correction.

[0052] Environmental and performance characteristics can include a variety of parameters. For example, environmental characteristics can include ambient temperature or even the temperature of specific components of the mass spectrometer. The temperatures of inductors 130a and 130b, and the temperatures of the poles 125a-d of quadrupole 120, affect the inductance and capacitance of the resonant circuit, respectively, and therefore any temperature variation will affect the amplitude of the RF signal applied to the poles 125a-d. Therefore, controller circuitry 135 can apply an amplitude correction factor by adjusting RF input 105 to account for component temperatures, resulting in an amplitude of RF signal 160 that is closer to the expected amplitude. Additionally, the temperature of any readback circuitry (e.g., ADC 140) or RF amplifier 110 can be determined and used to modify the actual amplitude of RF signal 160 to achieve a correction toward the expected amplitude.

[0053] Performance characteristics can include how the mass spectrometer is used. For example, the quadrupole can operate in scan mode or skip mode. Full scan MS is an example of scan mode, while SIM and SRM are examples of skip mode. In scan mode, the RF signal 160 is continuously varied from the starting m / z point to the ending m / z point at a specific scan rate. In skip mode, the RF signal 160 is stepped to a voltage at a specific m / z and held, or slowly tilted over a narrow m / z range. The RF signal 160 is then changed or skipped to a voltage for the next m / z, and this is repeated until all desired ions have been analyzed. As a result, specific operating modes, scan rates, starting m / z points, and ending m / z points (or corresponding voltages or amplitudes) can be used. Therefore, when the actual amplitude of the RF signal 160 is determined by the controller circuitry 135, the quadrupole 120 of the mass spectrometer is determined and used to apply an amplitude correction factor to the RF input 105 (e.g., by changing the amplitude of the RF input 105).

[0054] Current performance characteristics and environmental characteristics, as well as the amplitudes of RF input 105 and RF signal 160, can also be added to the LUT. This allows the controller circuitry 135 to continuously store data about performance and environmental characteristics, actual amplitude, and how amplitude correction is applied to RF input 105 (e.g., at what amplitude should RF input 105 be driven).

[0055] By utilizing a digital circuit system implemented by controller circuit 135 and ADC 140, many functions can be achieved, allowing for more precise control of the actual amplitude of the RF signal 160, improving the stability and calibration of the mass spectrometer, and enabling additional control strategies, as discussed later in this paper.

[0056] As previously mentioned, the analytical DC voltage is also applied to the quadrupole. If the actual analytical DC voltage differs from the expected analytical DC voltage, the controller circuit 135 can also adjust the analytical DC voltage applied to the poles 120a-d. Figure 3An example of digital control of analytical DC voltage is shown. Figure 4 An example block diagram of digital control for analytical DC voltage is shown. In Figure 4 In this process, the analytical DC voltage (405) applied to the quadrupole can be determined. Figure 3 In this configuration, the analytical DC voltage driver 305 provides a DC voltage signal 310 by generating a specific analytical DC voltage required by the quadrupole 120 to manipulate the electric field for ions. A voltage divider 315 divides or scales the voltage down to a level safely accessible to the controller circuitry 135, which can then determine the actual voltage of the DC voltage signal 310.

[0057] Back Figure 4 The actual voltage is compared with the expected voltage (410) to determine the current performance and environmental characteristics (415), and the current and historical performance and environmental characteristics are used to determine the DC voltage correction (420). The DC voltage correction is then used to adjust the DC voltage (425). For example, in Figure 3 In this process, the DC voltage input 320 is adjusted so that how the analytical DC voltage driver 305 drives or generates the DC voltage signal 310 is changed, so that an appropriate analytical DC voltage is applied to the rod. Although the analytical DC voltage has been discussed in the foregoing example, the DC offset applied to the rod can also be controlled in a similar manner to set the kinetic energy of the ions passing through the quadrupole.

[0058] Additional functions initiated by controller circuit 135 include determining how the resonant circuit should operate. Figure 5 An example of determining the characteristics of a resonant circuit is shown. Figure 6 An example of a block diagram used to determine the characteristics of a resonant circuit is shown. Figure 6 In this process, the pulse waveform is provided to the amplifier (605). For example, in Figure 5 In this circuit, controller circuit 135 can generate pulse waveform 510 (e.g., a short-duration voltage pulse) as input to RF amplifier 105. Next, in... Figure 6 In this process, the RF signal 160 is digitized (610) and the resonant frequency of the resonant circuit is determined (615). For example, in Figure 5 In this circuit, the frequency 505 of the RF signal 160 is determined by digitizing the RF signal 160 using an ADC 140. This allows for determining the frequency at which the resonant circuit should resonate, and allows for the observation of harmonics that may indicate problems such as electrical crosstalk from other electrical components. The frequency of the RF signal 160 provided by the amplifier 110 through the inductor 130b should be the same as or similar to the resonant frequency, and therefore, in Figure 6 In this configuration, the frequency of the RF amplifier input signal (620) can be adjusted. For example, the frequency of the RF input signal 105 can be set to... Figure 5The resonant frequencies are the same. Therefore, the controller circuit 135 can adjust not only the amplitude of the RF input signal 105 (and subsequently the RF signals 115, 155 and 160), but also the frequency of the RF input signal 105 (and therefore the RF signals 115, 155 and 160).

[0059] RF signals can be digitized at the two terminals of an inductor to provide additional information and adjustments. Figure 11 This illustrates another example of digital control over the amplitude of the RF signal generated by the amplifier. Figure 11 In this circuit, both RF signals 115 and 160 can be provided by controller circuit 135 to ADC 140 (or a separate ADC) for digitization and use. That is, the RF signals at the two terminals of coil 130a (and / or 130b) can be digitized and used to adjust RF input signal 105.

[0060] For example, Figure 5 The pulse waveform 510 in the middle is used as Figure 11 The RF input signal 105 is provided to the RF amplifier 110, and both RF signals 115 and RF signals 160 can be digitized. By digitizing the RF signals at the two terminals of the inductor 130b, more information about the individual inductor and capacitor components of the resonant circuit can be identified.

[0061] As previously described, a resonant circuit is achieved through the inductance of the inductor coil and the capacitance of each pole of the quadrupole. Therefore, the variation in inductance of the inductor coil (e.g., inductor 130b) can be independently determined by analyzing the RF signals at the two terminals of the inductor coil. For example, the phase difference between RF signals 115 and 160 can be determined. This explains some variation in the resonant frequency. However, any remaining variation is explained by the variation in capacitance. The variation in capacitance represents a change in the geometry of the corresponding quadrupole, which can cause mass drift due to the inappropriate generation of an oscillating electric field. Therefore, the controller circuit 135 can determine the variation in inductance, explain the remaining variation in the resonant frequency and correlate it with the variation in capacitance, and then adjust accordingly. Figure 11 The RF input signal 105 is used. Additionally, the controller circuit 135 can adjust the resolved DC voltage (e.g., Figure 3 DC voltage signal 310 in the middle.

[0062] Other techniques can also be used to determine the behavior of the resonant circuit. For example, the frequency of the RF signal 115 can be determined based on the operating frequency of the mass spectrometer. Figure 5 The pulse waveform 510 in the middle is used as Figure 11The RF input signal 105 is provided to the RF amplifier 110, and the frequency of the RF signal 160 is determined. Therefore, the frequency of the RF signal 160 can be compared with the operating frequency of the mass spectrometer to determine the change in resonant frequency due to the change in inductance.

[0063] Furthermore, how the resonant circuit currently operates, and how it has operated in the past (e.g., by recording the results of the resonant frequency when a pulse waveform is provided), can be used to determine the health status of the mass spectrometer. For example, harmonic identification can be used to identify faulty capacitors or inductors, including the inductors in the resonant circuit. When the resonant frequency is determined, component degradation over time can be identified. Additionally, any of the aforementioned information determined in this example (e.g., the amplitude of the RF signal 160) can be stored and used to determine the health status of the mass spectrometer. Based on this health status, alarms indicating that the mass spectrometer requires maintenance can be generated (e.g., via a graphical user interface (GUI) on a monitor communicatively coupled to the mass spectrometer, via email or other communications, etc.), or even how the mass spectrometer operates can be adjusted. For example, the timing of operations (e.g., scan time) can be adjusted based on health information, as can the voltage applied to components. In another example, the temperature of components (e.g., inductors or quadrupoles) can be adjusted (e.g., cooled or heated respectively via temperature control devices such as fans or heaters) based on health information, because this health information affects the amplitude of the RF signal, as previously described.

[0064] If any amplitude drift occurs, the amplitude adjustment of the RF signal 160 can be constantly monitored and maintained at the expected amplitude. However, in some implementations, the controller circuit 135 may not make an adjustment if the difference between the actual amplitude and the expected amplitude is less than a threshold amount. Adjustment can be performed because there may be some small variations due to noise, and maintaining the amplitude itself will not significantly affect the performance of the quadrupole 120.

[0065] In some implementations, the amplitude of the RF signal at the fundamental frequency can be identified. For example, using digital signal processing (DSP) techniques such as Discrete Cosine Transform (DCT), the RF signal captured in the time domain using an ADC can be represented in the frequency domain. This provides the frequency components of the RF signal. Because the fundamental frequency is the lowest frequency of a periodic waveform, and harmonics are multiples of the frequency, the fundamental frequency can be identified separately from the harmonics, and therefore the amplitude of the frequency components at the fundamental frequency can be determined. By identifying the amplitude without harmonics, more precise adjustment of the RF signal can be performed.

[0066] Figure 8 An example block diagram is shown illustrating digital control of the amplitude of an RF signal by identifying harmonics. Figure 8In this process, the RF signal is digitized (805), and the fundamental frequency of the RF signal is identified (810). For example, a DCT is applied to the digital representation of the RF signal, effectively transforming the digital representation from the time domain to the frequency domain to display the amplitude of the frequency components of the RF signal. Alternatively, a Discrete Fourier Transform (DFT) or a Fast Fourier Transform (FFT) can be applied. The fundamental frequency and its harmonics can be identified from the frequency components, and the amplitude of the frequency components at the fundamental frequency can be identified (815). For example, the lowest frequency can be the fundamental frequency. The amplitude of the frequency components at the fundamental frequency can then be compared with the expected amplitude of the RF signal (820). That is, a harmonic-free amplitude comparison can be performed by comparing the amplitude of the frequency components at the fundamental frequency with the amplitude of the RF input 105. The amplitude of the RF signal can then be adjusted based on the comparison, for example, in a manner similar to that described above (825).

[0067] The controller circuit can also identify and adjust other characteristics of the RF signal 160. For example, the phase of the RF signal 160 may differ from what is expected (e.g., from the phase of the signal used to drive the RF amplifier) ​​due to harmonics. This is because the capacitance and inductance of the resonant circuit change with temperature, and the resonant frequency changes with time. Therefore, the frequency of the RF signal 160 may deviate from the resonant frequency of the resonant circuit, causing a phase difference. This, in turn, leads to an increase in the amount of harmonic content. Therefore, by determining the phase of the RF signal 160, the controller circuit can adjust the frequency of the RF input 105 to drive the RF amplifier 110 in a different way, so that the RF signal 160 is tuned to better match the expected values. Thus, in addition to adjusting the amplitude of the RF signal 160 to match the expected values, the frequency can also be adjusted to account for changes in the resonant frequency.

[0068] Figure 9 An example of a block diagram illustrating digital control of an RF signal by identifying phase differences is shown. Figure 9 In this process, the RF signal is digitized (905), and the phase difference between the actual phase and the expected phase of the RF signal is identified (910). For example, the phase difference between the RF signal 160 used to drive the RF amplifier 110 and the RF input 105 can be determined. Based on the phase difference, the frequency of the RF signal is adjusted (915). For example, the frequency of the RF input 105 can be changed so that the RF amplifier 110 is driven in different ways, resulting in changes in the frequencies of the RF signals 115, 155, and 160. The frequency change of the RF input 105 can be based on the phase difference between the actual phase and the expected phase of the RF signal 160.

[0069] In addition to determining the phase difference, the amount of harmonic content in the RF signal 160 can also be determined and used to adjust the RF signal 160. For example, as previously described, by using DSP technology such as DCT, various techniques, including determining the total harmonic distortion (THD), can be used to identify the different frequency components of the RF signal 160. This provides values ​​for the harmonic components of the RF signal 160, but other techniques can also be used to relay the amount of harmonic content to specific values ​​(e.g., the number of harmonic frequency components, etc.). Therefore, if the amount of harmonic content exceeds a threshold, the frequency of the RF signal 160 can be changed. As the RF signal 160 is adjusted to be closer to the resonant frequency of the resonant circuit, the amount of harmonic content will decrease. Therefore, when the RF signal 160 is sampled by the ADC, the amount of harmonic content can be repeatedly determined and used to adjust the frequency until the amount of harmonic content is below the threshold amount.

[0070] If excessive harmonic content is identified, this may indicate a poor health condition of components in the mass spectrometer, such as a problem with the coils of a resonant circuit causing the RF signal 160 frequency to deviate significantly from its resonant frequency. Therefore, as mentioned earlier, an alarm indicating that the mass spectrometer requires maintenance can be generated.

[0071] In some implementations, controller circuitry 135 can also adjust RF input 105 by introducing out-of-phase harmonic signals to eliminate or reduce harmonics in RF signal 160. For example, if the second harmonic is identified by frequency components, a 180-degree out-of-phase signal can be generated by controller circuitry 135 and superimposed on RF input 105. Due to the resulting destructive interference, this out-of-phase signal can attenuate the second harmonic observed in RF signal 160. Therefore, the amount of harmonic content can be reduced, and more precise control over the quadrupole (or another component) can be provided.

[0072] In some implementations, RF amplifier 110 can operate in a non-linear or overdriven manner to quickly achieve a steady-state RF signal. Based on the degree of overdrive and the current phase difference between RF signal 160 and the expected phase (or the phase of RF input 105), the phase of RF input 105 can be shifted to overdrive RF amplifier 110 for a faster transition to steady state. After achieving steady-state RF signal 160, the phase of RF input 105 can, for example, be shifted back to the resonant frequency.

[0073] Figure 7 An example of a mass spectrometer that digitally controls the amplitude of an RF signal generated by an amplifier is shown. Figure 7In this example, the mass spectrometer includes an ion source 710, a quadrupole mass analyzer 720, a detector 715, an RF amplifier circuit 740, and a controller circuit 705. The controller circuit 705 includes or has access to a memory storing instructions for performing the techniques described in the examples, as well as any information for performing the techniques. The RF amplifier circuit 740 includes the circuit system described in the examples, including a resonant circuit, an amplifier, and an amplitude control circuit.

[0074] Ion source 710 receives analyte 725, such as a peptide received from a separation device like a liquid chromatography (LC) system, and ionizes the received peptide to form ions. However, other types of analytes can be received, and other separation techniques, such as gas chromatography (GC) or capillary electrophoresis (CE), can also be used. The ions are then mass-analyzed using a mass analyzer 720 (e.g., a quadrupole). Detector 715 generates a signal representing m / z, which is interpreted by controller circuitry 705 to generate or determine information that can be used to generate a mass spectrometer. Other types of mass spectrometers, such as tandem mass spectrometers, can also be used.

[0075] Although quadrupole mass analyzers and filters are described in the examples, other types of mass analyzers and filters can be used with the techniques described herein. Additionally, other components of mass spectrometers that use RF signals, such as ion directors, ion traps (including 3D ion traps, linear ion traps, etc.), other multipole assemblies (including hexapoles or octaapoles), stacked ring ion directors, ion funnels, etc., can also be used with the techniques described herein.

[0076] Figure 10 Examples of electronic devices that can be used to implement some of these embodiments are shown. In some implementations, Figure 10 An electronic device may store or use a computer program product including one or more non-transitory computer-readable media in which computer program instructions are stored, the computer program instructions being configured such that, when executed by one or more computing devices, the one or more computing devices perform the techniques described herein.

[0077] exist Figure 10 In this document, computer system 1100 can implement any of the methods or techniques described herein. For example, computer system 1100 can implement... Figure 7The controller 705 is included. Therefore, the operation of the associated mass spectrometer components can be adjusted based on calculations or determinations performed by the computer system 1100. In various embodiments, the computer system 1100 may include a bus 1102 or other communication mechanism for conveying information, and a processor 1104 coupled to the bus 1102 to process information. In various embodiments, the computer system 1100 may also include: a memory 1106 coupled to the bus 1102, which may be random access memory (RAM) or other dynamic storage device; and instructions to be executed by the processor 1104. The memory 1106 may also be used to store temporary variables or other intermediate information during the execution of instructions to be executed by the processor 1104. In various embodiments, the computer system 1100 may further include a read-only memory (ROM) 1108 or other static storage device coupled to the bus 1102 to store static information and instructions of the processor 1104. A storage device 1110, such as a magnetic disk or optical disk, may be provided and coupled to the bus 1102 to store information and instructions.

[0078] In various embodiments, the computer system 1100 can be coupled to a display 1112, such as a cathode ray tube (CRT) or liquid crystal display (LCD), via a bus 1102 to display information to the computer user. An input device 1114, including alphanumeric keys and other keys, can be coupled to the bus 1102 to transmit information and command selections to the processor 1104. Another type of user input device is a cursor control 1116, such as a mouse, trackball, or cursor arrow keys, which transmits directional information and command selections to the processor 1104 and controls cursor movement on the display 1112. Such an input device typically has two degrees of freedom on two axes (a first axis (i.e., x) and a second axis (i.e., y)), which allows the device to specify a position in a plane.

[0079] Computer system 1100 can perform the techniques described herein. Consistent with certain embodiments, computer system 1100 can provide results in response to processor 1104 executing one or more sequences of one or more instructions contained in memory 1106. Such instructions can be read into memory 1106 from another computer-readable medium, such as storage device 1110. Executing the sequence of instructions contained in memory 1106 can cause processor 1104 to perform the processes described herein. In various embodiments, the instructions in memory can be ordered to use various combinations of logic gates available within the processor to perform the processes described herein. Alternatively, a hard-wired circuit system can be used in place of or in combination with software instructions to implement the teachings of this invention. In various embodiments, the hard-wired circuit system may include the necessary logic gates that operate in the necessary order to perform the processes described herein. Therefore, the embodiments described herein are not limited to any particular combination of hardware circuit systems and software.

[0080] As used herein, the term "computer-readable medium" refers to any medium that participates in providing instructions to processor 1104 for execution. Such media can take many forms, including but not limited to non-volatile media, volatile media, and transport media. Examples of non-volatile media include, but are not limited to, optical discs or magnetic disks, such as storage device 1110. Examples of volatile media include, but are not limited to, dynamic memory, such as memory 1106. Examples of transport media include, but are not limited to, coaxial cables, copper wires, and optical fibers, including conductors containing bus 1102.

[0081] Common forms of non-transitory computer-readable media include, for example, floppy disks, floppy disks, hard disks, magnetic tapes or any other magnetic media, CD-ROMs, any other optical media, punched cards, paper tapes, any other physical media with a perforated pattern, RAM, PROMs and EPROMs, flash EPROMs, any other memory chips or boxes, or any other tangible media that a computer can read.

[0082] According to various embodiments, instructions configured to be executed by a processor to perform a method are stored on a computer-readable medium. The computer-readable medium may be a device for storing digital information. For example, the computer-readable medium includes a compressed optical disc read-only memory (CD-ROM) as known in the art for storing software. The computer-readable medium is accessed by a processor adapted to execute the instructions configured to be executed.

[0083] In various embodiments, the methods taught in this invention can be implemented in software programs and applications written in conventional programming languages ​​such as C and C++.

[0084] While the technology has been described in conjunction with various embodiments or examples, it is not intended to be limited to these embodiments. Rather, the technology encompasses various alternatives, modifications, and equivalents, as will be understood by those skilled in the art.

[0085] Furthermore, in describing the various embodiments, this specification may have presented methods and / or processes in a specific sequence of steps. However, the methods or processes should not be limited to the specific sequence of steps described herein, to the extent that they do not depend on the specific order of steps set forth herein. Other sequences of steps are also possible, as will be understood by those skilled in the art. Therefore, the specific order of steps set forth herein should not be construed as limiting the claims. Additionally, the claims for the methods and / or processes should not be limited to performing the steps in the written order, and those skilled in the art will readily understand that the sequence can be modified while still remaining within the spirit and scope of the various embodiments.

[0086] The embodiments described herein can be practiced with other computer system configurations including handheld devices, microprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, mainframe computers, etc. The embodiments can also be practiced in distributed computing environments where tasks are performed by remote processing devices connected via a network.

[0087] It should also be understood that the embodiments described herein can employ various computer-implemented operations involving data stored in a computer system. These operations are operations that require physical manipulation of physical quantities. Typically, but not necessarily, these quantities take the form of electrical or magnetic signals that can be stored, transferred, combined, compared, and otherwise manipulated. Furthermore, the manipulations performed are typically explicitly referred to as generating, identifying, determining, or comparing, etc.

[0088] Any operation forming part of the embodiments described herein is a useful machine operation. The embodiments described herein also relate to means or apparatus for performing these operations. The systems and methods described herein can be specifically configured to achieve a desired purpose, or they can be general-purpose computers selectively activated or configured by computer programs stored in a computer. Specifically, various general-purpose machines can be used with computer programs written in accordance with the teachings herein, or it may be more convenient to construct more specialized devices for performing the desired operations.

[0089] Some embodiments may also be embodied as computer-readable code on a computer-readable medium. A computer-readable medium is any data storage device that can store data that can subsequently be read by a computer system. Examples of computer-readable media include hard disk drives, network attached storage (NAS), read-only memory, random access memory, CD-ROM, CD-R, CD-RW, magnetic tape, and other optical and non-optical data storage devices. Computer-readable media may also be distributed across a network-coupled computer system, such that the computer-readable code is stored and executed in a distributed manner.

Claims

1. A mass spectrometer comprising: Quadrupole mass analyzer; An amplifier circuit configured to generate a first RF signal based on an amplifier radio frequency (RF) input signal; A circuit configured to receive the first RF signal and generate a second RF signal applied to a pair of bars of the quadrupole mass analyzer; Analog-to-digital converter (ADC), the analog-to-digital converter being configured to receive the second RF signal and generate a digitized second RF signal; and The controller circuit is configured to: Receive the digitized second RF signal; The actual amplitude of the second RF signal is determined based on the digitized second RF signal; It is determined that the actual amplitude of the second RF signal is different from the expected amplitude of the second RF signal; Determine the current environmental parameters and current performance parameters of the mass spectrometer; The amplitude correction applied to the amplifier's RF input signal is determined based on the actual amplitude, the current environmental parameters and current performance parameters, as well as historical environmental and performance parameters. The amplifier RF input signal is adjusted according to the amplitude correction so that the actual amplitude of the second RF signal is adjusted to the expected amplitude.

2. The mass spectrometer of claim 1, wherein the current environmental parameters include the temperature of the components of the mass spectrometer.

3. The mass spectrometer of claim 2, wherein the component is one or more of the following: an inductor of a resonant circuit, or one or both of the pairs of bars of the quadrupole mass analyzer.

4. The mass spectrometer according to claim 1 or 2, wherein the current performance parameters include the operating mode of the quadrupole mass analyzer.

5. The mass spectrometer according to claim 1 or 2, wherein the controller circuit is further configured to: Determine the DC voltage applied to one or both bars of the pair of bars of the quadrupole mass analyzer; Determine that the DC voltage is different from the expected DC voltage; and Adjust the DC voltage to be closer to the expected DC voltage.

6. The mass spectrometer of claim 5, wherein the DC voltage is adjusted to be closer to the expected DC voltage based on the historical environment and performance parameters.

7. The mass spectrometer according to claim 1, wherein the controller circuit is further configured to: Determine the characteristics that indicate how the resonant circuit should function; and The second RF signal is adjusted based on the determination of the characteristics that indicate how the resonant circuit should perform.

8. The mass spectrometer of claim 7, wherein determining the characteristic indicative of how the resonant circuit performs comprises: Provide pulse waveforms to the amplifier circuit; as well as The resonant frequency of the resonant circuit is determined based on the frequency of the second RF signal generated in response to the pulse waveform.

9. The mass spectrometer of claim 1, wherein the controller circuitry includes defined digital logic for implementing the amplitude correction.

10. An apparatus comprising: An amplifier circuit, configured to drive the electrodes of a mass spectrometer component based on an amplifier radio frequency (RF) input signal; and A controller circuit configured to provide the amplifier RF input signal in response to determining that the actual amplitude of the RF signal differs from the expected amplitude, the controller circuit determining one or both of the current environmental characteristics or current performance characteristics of the mass spectrometer, and providing the amplifier RF input signal based on one or both of: (i) a comparison of the current environmental characteristics of the mass spectrometer with past environmental characteristics stored in a memory, or (ii) a comparison of the current performance characteristics with past performance characteristics stored in the memory.

11. The device of claim 10, wherein the current environmental characteristics and the past environmental characteristics include the temperature of the components of the mass spectrometer.

12. The device of claim 11, wherein the component is one or more of the following: a multipolar assembly, an ion director, an ion trap, a stacked ring ion director, or an ion funnel.

13. The device of claim 10, wherein the inductor is configured to provide the RF signal to drive the electrodes of the component, and to provide the amplifier RF input signal based on a comparison of the current temperature and past temperature of the inductor.

14. The device of claim 10, wherein the past performance characteristics include how the mass spectrometer performs during operating modes.

15. The device of claim 10, wherein the component is a quadrupole mass filter.

16. A method comprising: A generator RF input signal is generated to drive an amplifier circuit, which is configured to apply the RF signal to a multipole quality analyzer. The controller circuit determines that the actual amplitude of the RF signal is different from the expected amplitude of the RF signal; The controller circuit identifies one or both of the following: (i) the current environmental characteristics and past environmental characteristics of the multi-pole quality analyzer, or (ii) the current performance characteristics and past performance characteristics of the multi-pole quality analyzer, wherein the past environmental characteristics and past performance characteristics are stored in memory; and The amplifier RF input signal is adjusted by the controller circuit taking into account one or both of the following: (i) a comparison of the current environmental characteristics and past environmental characteristics of the multipole quality analyzer, or (ii) a comparison of the current performance characteristics and past performance characteristics of the multipole quality analyzer.

17. The method of claim 16, wherein the current performance characteristics and past performance characteristics include one or more of the following: the scan rate of the mass spectrometer, or the operating mode of the mass spectrometer.

18. The method of claim 16, wherein the current environmental characteristics and past environmental characteristics include the temperature of the components of the mass spectrometer containing the multipole mass analyzer.

19. The method of claim 18, wherein the component is one or more of the following: an inductor configured to apply the RF signal to the resonant circuit of the multipole mass analyzer, a rod of the multipole mass analyzer, an ion guide, an ion trap, a stacked ring ion guide, or an ion funnel.

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