Amplifier arrangement for an ion-optical device

Abstract

Amplifier arrangement for providing a varying electrode voltage to an ion-optical device. The amplifier arrangement comprises: a high-speed amplifier configured to receive an input signal at the amplifier arrangement and provide a low-voltage output signal; and a slowly adjustable voltage source arranged to float on the low-voltage output and configured to provide a high-voltage output signal to the amplifier arrangement. The high-voltage output signal of the amplifier arrangement is fed back to control the high-speed amplifier. Advantageously, the amplifier arrangement forms part of a power supply for providing the varying electrode voltage, for example, as part of an ion analysis system.

Description

Technical area of ​​disclosure The disclosure relates to an amplifier arrangement for providing a varying electrode voltage for an ion-optical device, a power supply comprising such an amplifier arrangement, and an ion analysis system (for example, a mass spectrometer) comprising such a power supply. Background to the disclosure In a time-of-flight (TOF) mass spectrometer, the flight times of ions traveling a known distance are recorded. These flight times are used to determine the mass-to-charge (m / z) ratios of the ions. In contrast, Fourier transform mass spectrometry (FTMS), including orbital trap system mass spectrometry, uses a design in which the ions move cyclically within an ion trap. A measured vibrational frequency is used to determine the mass-to-charge ratios. Hybrid mass spectrometry uses various types of mass analyzers for tandem mass spectrometry, or MSn. An example of such a mass spectrometer is shown in Fig. 1 of GB2626803A. These types of mass spectrometers employ orthogonal m / z filtering (referred to as pre-filtering) to improve the mass analyzer's performance. This can be used to limit the amount of ions in the analyzer, thereby improving its performance, or to select specific ion species for further handling or fragmentation. A common pre-filter is a quadrupole mass filter. Ions migrating through an optical quadrupole ion device interact with electric fields generated by the superposition of RF and DC voltages. By controlling the ratio of the RF and DC voltages, it is possible to select ions with a specific m / z range. Alternatively, other types of multipole mass filters can be used. Another technique for increasing the analytical performance of a ToF mass analyzer is to select specific ion species within the analyzer by removing unwanted ions before they reach the detector. This can be achieved using electrostatic lenses, allowing the other ion species to be reflected multiple times without interacting with the unwanted species, thus significantly extending the trajectory of the ions being analyzed. Another approach uses a prism-like deflector to achieve a so-called "zoom mode". This is described in GB2617229A and GB2619766A (which also show a quadrupole mass filter and other ion-optical components and devices used for mass selection). These filtering techniques rely on DC voltages to select a desired m / z range of ions from the received ions, which are supplied, for example, by a power supply unit, as described in GB2617229A. The change in DC voltages should be as rapid as possible; that is, this requires a short voltage settling time. In the case of a quadrupole mass filter, the change can occur when selecting different m / z regions for successive scans. A longer switching time reduces the overall speed of the mass spectrometer. For in-flight ion selection using electrostatic lenses, a minimum voltage switching frequency is required to select the ions. The required settling time can vary from a few microseconds (µs) to several hundred microseconds.With a quadrupole (or other multipole) mass filter, a very precise adjustment in the range of a few tens of parts per million (ppm) may be required. In these examples, the voltages applied to the electrodes are not simply switched on or off, but precisely adjusted to different non-zero potentials (so that the change is made quickly and accurately). The target voltages in these applications are typically in the range of a few volts to a few kilovolts. Existing voltage amplifiers with such a high bandwidth (i.e., switching speed) combined with a high output voltage (and a wide output voltage range) are complex and consume a lot of power. It is therefore desirable to offer a voltage amplifier capable of quickly and precisely setting a high output voltage with low power consumption. Such a voltage amplifier would thus be well suited for use in a power supply to provide voltage to an electrode of an ion-optical device. Summary of Disclosure Against this background, an amplifier arrangement according to claim 1, a power supply for supplying at least one voltage to an electrode of an ion-optical device according to claim 10, and an ion analysis system according to claim 11 are provided. Further optional and / or advantageous features are defined in the dependent claims. The disclosure describes an amplifier design that enables fast and precise high-voltage adjustment with low power consumption. It is based on a compound amplifier design in which amplifiers with different characteristics are combined to achieve a combination of desired properties in a single circuit. In particular, a combination of a high-speed, low-voltage amplifier that enables precise adjustment (for example, in steps of one or more tenths of a volt or ten volts) and a low-speed, high-voltage amplifier (which may be a galvanically isolated power supply) that provides a high-voltage output (for example, about 1 kV) can realize the combined advantages of both amplifiers. The low-speed, high-voltage amplifier is advantageously connected as a floating stage on the output of the high-speed, low-voltage amplifier.Advantageously, the output of the low-speed high-voltage amplifier is used to control the high-speed low-voltage amplifier. Compound amplifier designs are well known. Examples include: amplifiers for driving high loads combined with precision amplifiers to achieve precise load driving; and fast amplifiers combined with precision amplifiers to achieve both high speed and precision. In all these examples, both amplifiers operate in a common voltage range. In contrast, the disclosed amplifier arrangement is based on two distinct voltage ranges: a high (but slowly changing) one and a low (but fast) one. This can be used to supply a DC voltage to ion optics (particularly mass spectrometers), where a varying high voltage is desirablely required and should be provided quickly. This amplifier arrangement advantageously enables the provision of a cost-effective and energy-efficient high-voltage power supply. In particular, the amplifier arrangement can be manufactured cost-effectively, has low power consumption (and is therefore energy-efficient), allows for precise control of the output voltage, has a fast voltage settling time, and enables simple active noise reduction. In one example, the high-speed amplifier is a differential amplifier. The amplifier input can then be connected to one terminal of the differential amplifier (the positive terminal) and the output of the high-voltage power supply to the other terminal (the negative terminal), optionally via a resistor. This creates feedback that can be used to control the output of the high-speed amplifier. The high-voltage power supply can be controlled based on the input signal to the amplifier arrangement and / or the output signal of the high-speed amplifier. For example, the output of the high-speed amplifier can be amplified (or buffered) and / or used to match the amplifier's input and generate a control signal for the high-voltage power supply. Implementations of the high-voltage power supply can include a voltage-controlled voltage source or a current source with a floating capacitor. The amplifier arrangement can be part of a power supply that provides at least one voltage to an electrode of an ion-optical device (for example, a multipole ion conductor, a mass filter or trap, or electrostatic lenses). The ion-optical device and the power supply can be part of an ion analysis system, for example, a mass spectrometer or an ion mobility spectrometer. In particular, the disclosure may be specifically applicable to a time-of-flight (TOF) mass spectrometer, a hybrid mass spectrometer, or a Fourier-transform mass spectrometer (FTMS). A particularly advantageous application may be for a variable-path ion analyzer, for example, a multi-reflection (TOF) mass spectrometer that includes an electrostatic lens and / or a deflector.The voltage applied to this lens and / or deflector can be selected for injection and / or extraction or (in a “zoom” mode) to reverse the ion drift direction. Brief description of the drawings The invention can be implemented in practice in many different ways, and preferred embodiments are now described only by way of example with reference to the accompanying drawings, in which: Fig. 1 shows a schematic circuit diagram of a basic amplifier arrangement according to the disclosure; Fig. 2 shows a schematic circuit diagram of a more complex amplifier arrangement according to the disclosure with a simple feedback configuration; Fig. 3 shows the theoretical, simulated, and measured output voltage over time for an amplifier arrangement according to the disclosure; Fig. 4 shows a circuit diagram of a first type of high-voltage source for use with embodiments according to the disclosure; Fig. 5 shows a circuit diagram of a second type of high-voltage source for use with embodiments according to the disclosure; and Fig.Figure 6 shows a schematic circuit diagram of a further amplifier arrangement according to the disclosure with a more sophisticated feedback configuration; Figure 7 shows a schematic representation of an analysis device that can be used in conjunction with the methods described herein; Figure 8 schematically shows further details of a mass spectrometer suitable for carrying out the approaches of various embodiments; Figure 9 schematically shows a detail of a first exemplary embodiment of a variable path length analyzer for use in the mass spectrometer of Figure 8; Figure 10 schematically shows a detail of a second exemplary embodiment of a variable path length analyzer for use in the mass spectrometer of Figure 8; and Figure 11 schematically illustrates a zoom operating mode for a variable path length analyzer. The use of the same reference symbol in different drawings is intended to indicate the same feature. Unless otherwise specified, drawings should be considered schematic. Detailed description of preferred embodiments With reference to Fig. 1, a schematic circuit diagram of a basic amplifier arrangement according to the disclosure is shown. The amplifier arrangement comprises the following: a high-speed, low-voltage (differential) amplifier U1, which controls the common potential of a high-voltage source V1. A voltage feedback resistor R1 measures the total voltage and closes the control loop by supplying the negative input of the low-voltage amplifier U1 with the high voltage. The input voltage for the amplifier is received at the positive input of the low-voltage amplifier U1. Accordingly, the output voltage of the circuit (at the output of the high-voltage source V1) is the sum of the output voltages generated by the low-voltage amplifier U1 and the high-voltage source V1. In effect, the high-voltage source V1 floats on the output of the low-voltage amplifier U1. While the high-voltage source V1 is slow to adjust, the low-voltage amplifier U1 can react quickly and not only rapidly change the output voltage but also compensate for overshoot, inaccuracies, and ripple caused by the high-voltage source V1. This switching concept defines two speed ranges: for small voltage fluctuations (e.g., up to approximately 40 V), the fast response of the low-voltage amplifier U1 is used to quickly change the voltage and allow it to settle rapidly. For larger adjustments (e.g., 40 V and above), the circuit can react as quickly as the high-voltage source V1. Such characteristics are well-suited for applications in ion optics, particularly in mass spectrometry. The amplifier arrangement advantageously forms part of a power supply for applying voltages to the electrodes of an ion-optical device, for example, as part of an instrument (as described in detail, for example, with reference to Fig. 7 below). One implementation utilizes the power supply for the electrodes of a multipole ground filter, for example, a quadrupole ground filter (e.g., as shown with reference to Fig. 8 discussed below or Fig. 1 of GB2626803A). In this case, the ground filter is typically operated to scan an entire m / z range in windows. These windows are usually close together, so that new isolation can be achieved by changing the potentials using a step function of the low-voltage amplifier U1 to select the new m / z range.The low-voltage amplifier U1 ensures that the desired output voltage settles quickly, so that the mass spectrometer can start the analysis with minimal delay between measurements. During the analysis, the high-voltage source V1 changes its output voltage to reset the output of the low-voltage amplifier U1 to zero, preparing it for the next voltage step. The change in the output voltage of the high-voltage source V1 is thus compensated by the output of the low-voltage amplifier U1, and the power supply to the electrodes of the quadrupole remains stable during this time. After the analysis is complete, the next voltage step would be applied. In this way, the scan speed of the quadrupole mass filter can be increased to such an extent that the high voltage source V1 continuously increases its voltage, while the low voltage amplifier U1 is operated in such a way that the total power remains stable for the time required by the mass filter. The operation of the power supply can be very similar for pre-filtering in a ToF mass analyzer (an example of this can be the ToF mass analyzer, in particular a multi-reflection ToF mass analyzer shown in Fig. 8 below or in Fig. 1 of GB2626803A). In general, an amplifier arrangement for providing a varying electrode voltage to an ion-optical device can be considered. The amplifier arrangement comprises: a high-speed amplifier configured to receive an input signal at the amplifier arrangement and provide a low-voltage output signal; and a slowly adjustable voltage source arranged to float on the low-voltage output and configured to provide a high-voltage output signal to the amplifier arrangement. In particular, the high-voltage output signal of the amplifier arrangement is fed back to control the high-speed amplifier. In some embodiments, the high-speed amplifier includes (or is) a differential amplifier. For example, the differential amplifier can be configured to receive the input signal to the amplifier arrangement at a first (negative) input and the high-voltage output signal of the amplifier arrangement at a second (positive) input (optionally via a resistor). In another aspect, a power supply for delivering at least one voltage to an electrode of an ion-optical device, comprising an amplifier arrangement disclosed herein, may be considered. In yet another aspect, an ion analysis system may be considered, comprising: an ion-optical device; and the power supply configured to deliver at least one voltage to an electrode of the ion-optical device. For example, the ion-optical device may be a multipole mass filter or may include electrostatic lenses. Advantageously, the ion-optical device is part of a mass spectrometer. The mass spectrometer may be one of the following: a time-of-flight (TOF) mass spectrometer; a hybrid mass spectrometer; and a Fourier-transform mass spectrometer (FTMS). Further details of specific embodiments will now be discussed. A further reference to the general aspects of disclosure explained above will then follow. Figure 2 shows a schematic circuit diagram of a more complex amplifier arrangement with a simple feedback configuration. Here, the output voltage of the circuit is advantageously regulated by cascaded controllers. An internal controller, based on the second amplifier U2, controls the high-voltage source V1. This second amplifier U2 receives the output of the low-voltage amplifier U1 via a second resistor R2 at its negative input, with its positive input connected to ground. The output of the second amplifier U2 is then provided as a control signal to the high-voltage source V1. The internal regulator thus aims for a zero-volt output voltage at the output of the low-voltage amplifier U1 to maximize U1's potential compensation capability. A second regulator (not shown) controls the low-voltage amplifier U1 to achieve the desired output voltage at the circuit's output. Reference is now made to Fig. 3, which shows the theoretical, simulated, and measured output voltage over time for an amplifier arrangement according to the disclosure (as shown in Figs. 1 and 2) with an example gain of 100. The upper graph shows the following: the steep rise of the input signal, increased by 100 for direct comparison (from 100.0 V to 110.0 V exactly at 100 ms); the slow step response for a simulated output of the high-voltage source V1, which has not yet reached 110 V even at 114 ms (because the high-voltage source V1 reacts too slowly to follow the step in the input); the simulated output of the amplifier arrangement, which quickly reaches 110.0 V within about 0.5 ms; and a measured output from an implementation of the amplifier arrangement. The lower diagram shows a simulated output voltage of the low-voltage amplifier U1, illustrating how it rises rapidly to compensate for the slow response of the high-voltage source V1, and then falls slowly as the power of the high-voltage source V1 increases (corresponding to the rate of change). As can be seen from Figures 1 and 2, the arrangement of the high-voltage source V1 and the low-voltage amplifier U1 causes the output of the amplifier arrangement to be the sum of the outputs of these individual circuits. Thus, the output of the low-voltage amplifier U1 compensates for the output of the high-voltage source V1. Effectively, the internal regulator adjusts the high-voltage source V1 so that the output of the low-voltage amplifier U1 can return to zero in order to be ready for the next rapid voltage change. The high-voltage source V1 could be implemented with one of many different designs. Referring to Fig. 4, a circuit diagram of a first exemplary type of high-voltage source for use with amplifier arrangements according to the disclosure is shown. This high-voltage source is formed by a power supply circuit, in this case a fully galvanically isolated power supply, which in this example provides an output power of up to 10 kV. The power supply consists of a self-resonant circuit coupled to a voltage multiplier via a transformer T1. The power supply receives a "drive" signal, a rectifier circuit, and a "noise cancel" signal and provides an output signal ("+HV"). The "drive" input relative to the circuit ground would be the voltage control input (which would also supply the power). The high voltage is then generated between the "noise cancel" and "+HV" terminals.The rectifier circuit includes a capacitor and a resistor arranged as a low-pass filter (LPF). Transformer T1 provides galvanic isolation. In this configuration, the "Noise_Cancel" signal can be driven by the output of the low-voltage amplifier U1. The low-voltage amplifier U1 only provides small output voltages (for example, in the range of ±20 V, ±12 V, ±10 V, or ±5 V), but the output voltage can be significantly lower (for example, in tenths of a volt or volts). Therefore, the isolation capability of transformer T1 does not need to be very high. It is usually already covered by the output voltage specifications, which in this example would be significantly higher than 20 V. This power supply, for example, has a self-resonant frequency of approximately 50 kHz. A large portion of the resulting output ripple is filtered out by the low-pass filter (LPF). This can result in a relatively clean voltage, but it further reduces the response time of the output voltage. The same applies to all other transformer-based designs, regardless of whether they are self-resonant or actively driven. An alternative implementation for the high-voltage source V1 can be based on a current source with a floating capacitor. Referring to Fig. 5, a circuit diagram of a second exemplary type of high-voltage source for use with amplifier arrangements according to the disclosure is shown. This circuit diagram is somewhat simplified, but shows the main components. The high-voltage source implementation shown in Fig. 5 comprises a cascode stage consisting of at least one optocoupler (in this case, two optocouplers U3 and U4) and one or more field-effect transistors (in this case, two n-type MOSFET transistors M1 and M2) that serve as current sources. The transistors provide the voltage rating and can be stacked to increase it. One arm of this arrangement could also be replaced by a high-voltage resistor. One end of a filter capacitor C2 is connected to the output of the low-voltage amplifier U1 via the "Noise_Cancel" terminal. Due to the high impedance of the current sources, the low-voltage amplifier U1 can shift the capacitor in a similar manner to the isolation transformer-based power supply circuit described above with reference to Fig. 4. Amplifier arrangements according to the disclosure can also be operated to reduce output noise. If a fast, small voltage step is desired (e.g., an additional 10 V to the originally generated 10 kV), this could be achieved by increasing the voltage supplied by the low-voltage amplifier U1. The output of the low-voltage amplifier U1 raises the output of the entire amplifier arrangement by 10 V, while the voltage across the output capacitor of the high-voltage source V1 (the capacitor in the low-pass filter LPF of the implementation in Fig. 4 or the capacitor C2 in the implementation in Fig. 5) remains constant. This results in a fast output step. The overall voltage regulator then adjusts the high-voltage source V1 to the new desired voltage, as explained above with reference to Fig. 3.This causes the low-voltage amplifier U1 to reduce its output from +10 V back to 0 V and be prepared for the next step. Such a scheme can also be useful for compensating for noise or voltage ripple, since the low-voltage amplifier U1 acts as a noise suppressor or step-down circuit. Even if a large portion of the residual ripple (e.g., from the self-resonant power supply) is filtered out, it can still be on the order of volts at the output. If the low-voltage amplifier U1 is a fast amplifier (which is easily achievable, at least due to the desired low output voltages), it can counteract the ripple and / or compensate for a further large portion of the residual ripple through self-resonance. This can enable very low-noise high voltages at very high frequencies. Providing a low-noise electrode potential at high voltage is highly desirable for mass spectrometers and is gaining increasing importance for achieving higher repetition rates in new ion-optical devices. For example, an ion mirror array for a mass analyzer (see, for example, Fig. 8, described below, or Fig. 1 of GB2626803A) can utilize a 6 kV voltage for proper ion deflection. The stability of this voltage can enable stable m / z measurements. For example, a voltage shift of 1.5 ppm can cause an m / z shift of 1 ppm. However, mass analyzers are designed for operation at very high rates, so maintaining such voltage stability at DC or very low frequencies limits the repetition rate of the analyzer.This is because the migration times of the ions can range from a few tens of microseconds to a few milliseconds, and stability on these timescales therefore becomes a limiting factor. It is also desirable to use each spectrum as an analysis result, and this prevents the smoothing out of higher-frequency disturbances by averaging the spectra. GB2630325A describes how high-voltage supply regulation can be implemented to achieve such stability, although response speed is not considered. This disclosure can be used to provide a precise and low-noise high-voltage output. In many applications, the need for a separate regulation regulator downstream of the high-voltage supply, as discussed in GB2630325A, could be reduced or eliminated. Referring to Fig. 6, a schematic circuit diagram of another example amplifier arrangement according to the disclosure with a more sophisticated feedback configuration is shown. This circuit diagram shows that the low-voltage amplifier U1 and the high-voltage source V1 are typically not controlled independently of each other. In this arrangement, the high-voltage source V1 comprises a power supply E1 along with an input low-pass filter formed by a resistor R2 and a capacitor C1. The low-voltage amplifier U1, providing a fast compensation voltage, consists of an amplifier A1 with an input resistor R6 and a feedback capacitor C3. It is evident that the output of the amplifier arrangement is the sum of the output of the low-voltage amplifier U1 and the output of the high-voltage source V1. The power supply E1 features a slow control circuit comprising a control amplifier U11, which receives a feedback signal via the feedback resistor R1. The faster, low-voltage amplifier U1 also has a second feedback resistor R5. In a real circuit, these could be combined to reduce the number of high-voltage dividers in the scheme. According to this control approach, both the low-voltage amplifier U1 and the high-voltage source V1 attempt to follow the input, and both are in a feedback loop with the output. A first control circuit around the low-voltage amplifier U1 attempts to directly achieve the desired output using the second feedback resistor R5. The control amplifier U11, which regulates the high-voltage source V1, also attempts to achieve the desired power. To balance these control loops, a connection is established between the output of the low-voltage amplifier U1 and the (negative) input of the control amplifier U11 via the circuit around a feedback amplifier U10, consisting of the input resistor R8, another feedback resistor R9, and the output resistor R7. The circuit around the feedback amplifier U10 generates an additional error signal for the control amplifier U11, which causes the feedback amplifier U10 to adjust (increase or decrease) the input voltage to the high-voltage source V1 until the output of the low-voltage amplifier U1 returns to zero.With this approach, the output voltage of the low-voltage amplifier U1 remains within its voltage range for smaller jumps, while the total power of the amplifier arrangement maintains the desired output voltage. Returning to the general aspects of the disclosure discussed above, some details must be considered. In particular, the slowly adjustable voltage source may be configured to be controlled by a control signal derived from the input signal at the amplifier arrangement and / or the low-voltage output signal of the high-speed amplifier. Specifically, the control signal may be derived from the input signal at the amplifier arrangement, which is adapted by a signal based on the low-voltage output signal of the high-speed amplifier. For example, a second (control) amplifier may be configured to receive a signal based on the low-voltage output signal of the high-speed amplifier as its input signal and generate the control signal based on the received signal.The signal based on the low-voltage output signal of the high-speed amplifier can be generated by a further (feedback) amplifier configured to receive the low-voltage output signal of the high-speed amplifier as its input signal. This second amplifier can then be configured to receive the input signal at the amplifier arrangement, which is adapted by the signal based on the low-voltage output signal of the high-speed amplifier (with both the input signal at the amplifier arrangement and the signal based on the low-voltage output signal of the high-speed amplifier being fed to a common node). In some embodiments, the slowly adjustable voltage source comprises a galvanically isolated power supply. For example, the slowly adjustable voltage source may comprise a voltage-controlled voltage source. Alternatively, the slowly adjustable voltage source may comprise a current source with a floating capacitor. Various designs are possible for the low-voltage amplifier U1. Typically, a fast operational amplifier with a buffer is used to increase the drive capability. Fig. 7 schematically illustrates an analytical apparatus, such as a mass spectrometer, which can be used in conjunction with the methods described herein. As shown in Fig. 7, the apparatus includes an ion source 10, a mass filter 20, a fragmentation device 30, and a mass analyzer 40. The ion source 10 is configured to generate ions from a sample. The ion source 10 can be coupled to a separation device (not shown), such as a liquid chromatography (LC) separator, a gas chromatography (GC) separator, or a capillary electrophoresis separator, and the like, so that the sample ionized in the ion source 10 comes out of the separation device. The ion source 10 can be any suitable ion source, such as an electrospray ionization (ESI) ion source, an atmospheric pressure ionization (API) ion source, a chemical ionization ion source, an electron impact (EI) ion source, or a similar source. Numerous other types of ionization are possible. The analytical device may additionally or alternatively include an ion separation device (not shown) located downstream of the ion source and configured to separate the ions of the samples according to a physicochemical property. For example, the device may include an ion mobility (IM) separator, a differential ion mobility separator, or a device configured to separate ions according to their mass-to-charge ratio (m / z). The mass filter 20 is arranged downstream of the ion source 10 and configured to receive ions from the ion source 10 (optionally via the ion separation device). The mass filter 20 is configured to filter the received ions according to their mass-to-charge ratio (m / z). The mass filter 20 can be configured such that received ions with m / z within an m / z transmission window (or "isolation window") of the mass filter are passed through the mass filter, while received ions with m / z outside the m / z transmission window are attenuated by the mass filter, i.e., not passed through the mass filter. The width and / or centering of the m / z transmission window can be controllable (variable), for example, by appropriately controlling the RF and / or DC voltage(s) applied to the electrodes of the mass filter 20.Therefore, the mass filter 20 can be operated, for example, in a transmission mode, in which most or all ions within a relatively wide m / z window are passed through the mass filter 20, and in a filtration mode, in which only ions within a relatively narrow m / z window (centered on a desired m / z) are passed through the mass filter 20. The mass filter 20 can be any suitable type of mass filter, such as a quadrupole mass filter. The fragmentation device 30 is located downstream of the mass filter 20 and is configured to receive most or all of the ions transmitted by the mass filter 20. The fragmentation device 30 can be configured to selectively fragment some or all of the received ions, i.e., to produce fragment ions. The fragmentation device 30 can operate in a fragmentation mode, in which most or all of the received ions are fragmented to produce fragment ions (which can then be passed on by the fragmentation device 30), and in a non-fragmentation mode, in which most or all of the received ions are passed on without being (intentionally) fragmented. It would also be possible to implement a non-fragmentation mode by causing ions to bypass the fragmentation device 30.The fragmentation device 30 can also be operated in one or more intermediate operating modes, e.g., where the degree of fragmentation is controllable (variable). The fragmentation device 30 can also be operated in higher-order fragmentation modes (MSN), e.g., where the fragmentions are further fragmented one or more times by the fragmentation device 30. The fragmentation device 30 can be any suitable type of fragmentation device, such as a collision-induced dissociation (CID) fragmentation device, an electron-induced dissociation (EID) fragmentation device, a photodissociation fragmentation device, and so on. Numerous other types of fragmentation are possible. The mass analyzer 40 is located downstream of the fragmentation device 30 and is configured to receive ions from the fragmentation device 30. Therefore, depending on the operating mode of the fragmentation device 30, the mass analyzer 40 can receive unfragmented precursor ions and / or fragment ions. The mass analyzer 40 is configured to analyze the received ions to determine their mass-to-charge ratio (m / z) and / or their mass, i.e., to generate a mass spectrum of the ions. The Mass Analyzer 40 can be any suitable type of mass analyzer, such as an ion trap mass analyzer, an electrostatic orbital trap mass analyzer (such as a Thermo Fisher Scientific Orbitrap™-FT mass analyzer), a time-of-flight (ToF) mass analyzer such as a multireflection time-of-flight (MR-ToF) mass analyzer, or a quadrupole mass analyzer. Numerous other types of mass analyzers are possible. It should be noted that Fig. 7 is merely a schematic representation and that the device may include, and in certain embodiments does include, any number of one or more additional components, such as ion-optical devices. For example, the device may include one or more ion transfer stages arranged between each of the components shown, including, for example, an atmospheric pressure interface and / or one or more ion conductors, lenses, and / or other optical ion devices configured to allow some or all of the ions to be adequately passed through the device. The ion transfer stage(s) may include any suitable number and configuration of ion-optical devices, for example, optionally including one or more ion conductors, lenses, and / or other ion-optical devices. In some embodiments, the device may include more than one mass analyzer. For example, the device may be a hybrid mass spectrometer with two mass analyzers of the type described in EP 3 410 463, the contents of which are incorporated herein by reference. As also shown in Fig. 7, the device is controlled by a control unit 50, such as a suitably programmed computer, which controls the operation of various components of the device and, for example, sets the voltages to be applied to the various components of the device. The control unit 50 can also receive and process data from various components, including the analyzer(s). The device can be operated in different operating modes. In particular, the device can be a tandem mass spectrometer that can be operated in an MS1 ​​operating mode and an MS2 operating mode. In the MS1 operating mode (or “full mass scan”), the mass filter 20 is operated in its transmission operating mode and the fragmentation device 30 in its non-fragmentation operating mode, so that, for example, a wide m / z range (e.g., the full mass range) of non-fragmented ions (“precursor ions” or “stem ions”) is analyzed by the analyzer 40 to generate an MS1 ​​spectrum. In the MS2 operating mode, the mass filter 20 is operated in its filter operating mode and the fragmentation device 30 in its fragmentation operating mode, so that, for example, a selected narrow m / z range of precursor ions is fragmented and the resulting fragment ions (“productions” or “daughter ions”) are analyzed by the analyzer 40 to generate an MS2 spectrum. The device can also be operated in one or more higher-order fragmentation modes, such as an MS3 operating mode in which precursor ions are fragmented, at least some of the resulting fragment ions are themselves fragmented, and the second-generation fragment ions (“grandchild ions”) are analyzed by the analyzer 40 to generate an MS3 spectrum. In general, the device can be operated in a fragmentation mode of any order, i.e., in an MSN operating mode with N ≥ 2. Fig. 8 schematically shows in more detail a mass spectrometer suitable for carrying out the procedures of various embodiments (corresponding to that shown in Fig. 7). The device is a hybrid device incorporating an MR-ToF analyzer 40 (of the type described in US Patent No. 9,136,101), a quadrupole mass filter 20, and an Orbitrap™ analyzer 60. The device also includes an electrospray source 10, a collision cell 30, and the various ion conductors, etc., for a complete mass spectrometer. It is understood that the device shown in Fig. 8 is a non-limiting example and that numerous variations are possible. In the embodiment shown in Fig. 8, the ion source 10 of the device is an electrospray ionization (ESI) ion source. The device includes a vacuum interface containing a transfer tube 21, an ion funnel 22, a quadrupole pre-filter ion conductor 23, and a so-called "bent flat-pole" ion conductor 24. The ion conductor 24 can be of the design described in U.S. Patent No. 9,536,722. The device also includes a mass filter in the form of a quadrupole mass filter 20, an ion trap 31 in the form of a curved linear ion trap (“C-trap”), and a collision cell 30 in the form of an ion routing multipole collision cell (“IRM”). Ions from the ion source 10 can be accumulated in the C-trap 31 and / or collision cell 30 by opening and closing a gating electrode located in a charge detector assembly 26 situated between the C-trap 31 and the mass filter 20. The apparatus includes a time-of-flight (ToF) mass analyzer 40 in the form of a multi-reflection ToF mass analyzer. In the apparatus shown in Fig. 8, the analyzer is of the inclined-mirror type described in US Patent No. 9,136,101, but it is understood that any type of ToF analyzer could be used. As shown in Fig. 8, the device includes a multipole ion conductor 32 to enable the transfer of ions from the collision cell 30 to the time-of-flight mass analyzer 40. The time-of-flight mass analyzer 40 includes an extraction trap 41, whereby ions are delivered from the collision cell 30 to the extraction trap 41 via the multipole ion conductor 32. The ions are accumulated and cooled in the extraction trap 41. The extraction trap 41 can comprise two trap regions: one with relatively high pressure for rapid ion cooling and a second low-pressure region for ion extraction. Ions are cooled in the high-pressure region and then transferred to the low-pressure region, where they are pulsedly ejected into the ToF analyzer via a pair of deflectors 42. Ions oscillate between a pair of mirrors 43 that are inclined relative to each other, so that the ion path is slowly deflected and reflected back to a detector 44. Correcting strip electrodes 45 counteract the loss of ion focus that would otherwise be induced by the non-parallelism of the mirrors. As also shown in Fig. 8, the device may optionally include a second mass analyzer in the form of an electrostatic mass analyzer 60, for example, an orbital ion trap mass analyzer, and more specifically, an orbital trapping or Orbitrap™-FT mass analyzer such as that manufactured by Thermo Fisher Scientific. This hybridized device is described in more detail in U.S. Patent No. 10,699,888, the contents of which are incorporated herein by reference. The ions can be collected in the ion trap 31 and then either ejected orthogonally to the orbital trap or to the Orbitrap™ analyzer 60 for analysis without entering the collision or reaction cell 30, or the ions can be transferred axially to the collision or reaction cell 30. Ions transferred to the collision or reaction cell 30 can either be fragmented by collisions with a collision gas and / or a reagent in the collision cell 30, or simply cooled by collisions with a gas at lower energies, causing the ions to fragment. Once the ions have accumulated in the collision cell 30, they can be ejected for analysis either into the mass analyzer 40 (via the multipole ion conductor 32) or into the orbital trapping or Orbitrap™ analyzer 60 (via the C-trap 31). Figures 9 and 10 schematically illustrate the details of exemplary embodiments of the analyzer 40 with variable path length. In these embodiments, the analyzer 40 is a multi-reflection time-of-flight (MR-ToF) mass analyzer that can be operated in a "normal" single-pass operating mode and a multi-pass "zoom" operating mode. As shown in Fig. 9 and Fig. 10, the multireflection time-of-flight analyzer 40 comprises a pair of ion mirrors 43a, 43b, spaced apart from each other and facing each other in a first direction X. The ion mirrors 43a, 43b are extended along an orthogonal drift direction Y between a first end and a second end. An ion source (injector) 41, which may be in the form of an ion trap, is arranged at one end (the first end) of the analyzer. The ion source 41 can be arranged and configured to receive ions from the fragmentation device 30. Ions can be accumulated in the ion source 41 before being injected into the space between the ion mirrors 43a, 43b. As shown in Fig. 9 and Fig. 10, ions can be injected from the ion source 41 with a relatively small injection angle or a relatively low drift velocity, creating a zigzag ion path with different oscillations between the mirrors 43a, 43b being spatially spaced apart. One or more lenses and / or deflectors can be arranged along the ion path between the ion source 41 and the ion mirror 43b, which the ions first encounter. For example, as shown in Figures 9 and 10, a first extraplanar lens 46, an injection deflector 42a, and a second extraplanar lens 47 can be arranged along the ion path between the ion source 41 and the ion mirror 43b, which the ions first encounter. Other arrangements are possible. In general, the one or more lenses and / or the one or more deflectors can be configured to appropriately condition, focus, and / or deflect the ion beam, i.e., to cause it to assume the desired path through the analyzer. The analyzer 40 also includes another deflector 42b, which is arranged along the ion path between the ion mirrors 43a, 43b. As shown in Fig. 9 and Fig. 10, the deflector 42b can be arranged at approximately the same distance between the ion mirrors 43a, 43b along the ion path after its first ion mirror reflection (in the ion mirror 43b) and before its second ion mirror reflection (in the other ion mirror 43a). The analyzer also includes a detector 44. The detector 44 can be any suitable ion detector configured to detect ions and to record, for example, an intensity and arrival time associated with the arrival of the ion(s) at the detector. Suitable detectors include, for example, one or more conversion dynodes, optionally followed by one or more electron multipliers and the like. In its “normal” operating mode, ions from the ion source 41 are injected into the space between the ion mirrors 43a, 43b in such a way that the ions assume a zigzag ion path with multiple reflections between the ion mirrors 43a, 43b in the X direction, while: (a) they drift along the Y direction from the deflector 42b towards the opposite (second) end of the ion mirrors 43a, 43b, (b) the drift direction reverses near the second end of the ion mirrors 43a, 43b, and then (c) drift back along the Y direction towards the deflector 42b. The ions can then be caused to move from the deflector 42b to the detector 44 for detection. In the analyzer of Fig. 9, the ion mirrors 43a, 43b are inclined with respect to the X and / or Y drift direction. Alternatively, it would be possible for only one of the ion mirrors 43a, 43b to be inclined, while the other ion mirror 43a, 43b is arranged parallel to the Y drift direction. Generally, the ion mirrors have a non-constant distance from each other in the X direction along most or all of their length in the Y drift direction. An electric field, resulting from the non-constant distance between the two mirrors, opposes the drift velocity of the ions toward the far end of the ion mirrors. This electric field causes the ions to reverse their drift velocity near the far end of the ion mirrors and drift back toward the deflector along the drift direction. The analyzer shown in Fig. 9 further comprises a pair of corrective strip electrodes 45. Ions moving along the drift length are slightly deflected at each passage through the mirrors 43a, 43b, and the additional strip electrodes 45 are used to correct the time-of-flight error caused by the varying distance between the mirrors. For example, the strip electrodes 45 can be electrically biased so that the period of ion oscillation between the mirrors is essentially constant over the entire drift length (despite the non-constant distance between the two mirrors). The ions are finally reflected back into the drift space and focused at the detector 44. Further details of the multi-reflection time-of-flight mass analyzer with inclined mirror shown in Fig. 9 are contained in US Patent No. 9,136,101, the contents of which are incorporated herein by reference. In the analyzer of Fig. 10, the ion mirrors 43a, 43b are parallel to each other. To cause the ions to reverse their drift direction velocity near the second end of the ion mirrors and drift back along the drift direction towards the deflector, the analyzer in this embodiment includes a second deflector 48 at the second end of the ion mirrors 43a, 43b. As shown in Fig. 10, in this embodiment a lens can be enclosed in the injection deflector 42a and / or in the deflector 42b. This allows the ion beam to propagate a short distance into the analyzer before encountering a long-focus lens that focuses the ion beam along its length. The lens can be an elliptical drift-focusing (converging) lens mounted within the deflector 42b. The second deflector 48, which can also enclose a lens, serves to reverse the beam direction while maintaining control over the focusing characteristics. Further details of the single-lens multiple reflection time-of-flight mass spectrometer from Fig. 10 are described in UK patent number GB 2 580 089, the contents of which are incorporated herein by reference. In the analyzers shown in Figures 9 and 10, the ion beam can spread relatively broadly (in the drift direction Y) for most of its trajectory. This contrasts, for example, with multireflection time-of-flight (MR-ToF) mass spectrometers, which use a series of periodic lenses to focus the ion beam along its entire trajectory, as described, for instance, in the article "A. Verenchikov et al., Journal of Applied Solution Chemistry and Modelling, 2017, 6, 1-22". A significant advantage of allowing the ion beam to spread broadly for most of its trajectory is the reduction of space charge effects, which can be a significant problem for time-of-flight analyzers, especially when analyzing labeled analytes. Nevertheless, the embodiments described herein are also applicable to other MR-ToF analyzer designs, such as the Verenchikov-type MR-ToF analyzer. In the embodiments shown in Figs. 9 and 10, the fact that the ion beam is relatively wide in the drift dimension Y means that the deflector 42b should be able to receive such a wide beam without clipping or uneven deflection. A suitable deflector design is a trapezoidal or prismatic deflector. Therefore, the deflector 42b can comprise a trapezoidal or prism-like electrode positioned above the ion beam and another trapezoidal or prism-like electrode positioned below the ion beam. The electrodes can be located outside the plane of deflection, which makes it easy to manufacture them wide enough to accommodate a broad ion beam (at least compared to conventional deflection plates that would be positioned on either side of the beam). The electrodes can be angled with respect to the ion beam such that when a suitable (DC) voltage is applied to the electrode(s), the resulting electric field induces a deflection in the ion beam. Ions can be exposed to a relatively strong electric field at the edges of the angled electrodes, which induces a deflection.Suitable deflection voltages are on the order of ± a few volts, ± a few tens of volts, or ± a few hundred volts. The deflector should be configured (and is in some embodiments) to cause the ion beam to be deflected by a desired (selected) angle. The angle by which the ion beam is deflected by the deflector can be adjustable, for example, by adjusting the magnitude of one or more (DC) voltages applied to the deflector. In embodiments, the multireflection time-of-flight (MR-ToF) mass analyzer can be operated in a multi-pass “zoom” mode. In this mode, the ions complete multiple cycles within the analyzer in the drift direction Y. Increasing the number of cycles N increases the length of the ion path traveled within the analyzer (between the injector 41 and the detector 44), thereby improving the analyzer's resolution. In the Verenchikov analyzer, this can be achieved by controlling a voltage across an entrance lens. For the models shown in Fig. 9 and Fig. 1, the following applies:In the 10 analyzers shown, the deflector 42b on the front of the analyzer, which is normally used to reduce the injection angle and / or to optimize the number of oscillations within a single drift pass, can (also) be used to reverse the drift direction velocity of the ions in such a way that the ions are caused to go through another cycle through the analyzer. Therefore, in a multi-pass “zoom” operating mode, ions are caused to traverse multiple (N) cycles within the analyzer 40, with the ions drifting in the Y direction from the deflector 42b (or the entrance lens) towards the opposite (second) end of the ion mirrors 43a, 43b in each cycle, and then back to the deflector 42b (or the entrance lens). In each cycle, the ions also undergo multiple reflections between the ion mirrors in the X direction. Therefore, in each cycle, the ions assume a zigzag ion path through the space between the ion mirrors 43a, 43b. In the analyzers shown in Figures 9 and 10, an initial cycle can be initiated by injecting ions from the injector 41 into the space between the ion mirrors 43a and 43b. The ions can be reflected in one of the ion mirrors 43b and then move towards the deflector 42b. An appropriate (e.g., relatively small) voltage can be applied to the deflector 42b such that the ions are caused to leave the deflector 42b in the direction of the other end of the ion mirrors. Upon leaving the deflector 42b, the ions assume a zigzag ionic path with multiple reflections between the ion mirrors 43a, 43b in the direction X, while: (a) they drift along the drift direction Y from the deflector 42b towards the second end of the ion mirrors, (b) they reverse the drift direction velocity near the second end of the ion mirrors, and (c) they drift back along the drift direction Y to the deflector 42b. After the ions have completed this initial cycle, each subsequent cycle is initiated by using deflector 42b to reverse the drift velocity of the ions (near the first end of the ion mirrors). This can be achieved by applying a suitable voltage to deflector 42b, causing the ions to exit deflector 42b with a drift velocity opposite to the velocity at which they originally entered. This voltage can be applied over a period of time during which the ions are expected to return to deflector 42b. Suitable deflection voltages for reversing the drift direction of the ions are on the order of a few hundred volts. The deflector can be used to reverse the drift direction of the ions one or more times. Therefore, the procedure can involve causing the ions to complete multiple (N) cycles within the analyzer, with the first cycle being initiated by injecting the ions into the space between the ion mirrors, and after the ions have completed the first cycle, each subsequent cycle can be initiated by using the deflector to reverse the drift direction of the ions. After the ions have completed the desired (multiple) number (N) of cycles within the analyzer, they can migrate from the deflector 42b to the detector 44, where they are detected. For this purpose, a suitable voltage can be applied to the deflector 42b so that the ions leave the deflector 42b in the direction of the detector 44. The ions can be reflected in one of the ion mirrors 43a before moving to the detector 44 (and being detected by it). Fig. 11 schematically illustrates this zoom operating mode. As shown in Fig. 11, the ions from the ion trap source 41 are injected through a deflector 42a and between the mirrors at a relatively steep angle. After the first half-oscillation, the ions pass through a second prismatic deflector 42b, which reduces the injection angle by almost half. The oscillating ions then travel up the length of the extended mirror and are reflected back, for example, by the set inclination of the mirrors in the case of the analyzer in Fig. 9. At the point when the ions return to this second deflector 42b, the voltage can be switched from an injection / extraction potential of about -150 V to a capture potential of about +350 V, which reflects the ion beam back into the analyzer body for a second pass.After a desired number of passes (N) have been traversed by the ions, the deflector 42b is switched back to the injection / extraction potential and ions escape to the detector 44. In the general terms discussed above, the ion-optical device may comprise a variable-path ion analyzer (e.g., a multi-reflection time-of-flight mass analyzer) with an electrostatic lens and / or deflector, optionally located at the analyzer's inlet. The power supply may then be configured to provide a voltage to the electrostatic lens and / or deflector. Advantageously, the voltage applied to the electrostatic lens and / or deflector may be selected from the following: a first voltage that causes ions to be injected into and / or extracted from the variable-path ion analyzer; and a second voltage that reverses the drift velocity of the ions being analyzed by the variable-path ion analyzer. Although a number of embodiments have been described, experts will recognize that modifications and variations are possible. For example, different circuits can be implemented based on the principles explained above. Unless otherwise indicated by the context, singular forms of terms used in this document, including the claims, are to be interpreted as including the plural form, and vice versa. Unless the context indicates otherwise, for example, in the present document, including the claims, a singular reference such as "a" or "an" (such as an ion multipole device) means "one or more" (for example, one or more ion multipole devices). In the description and claims of this disclosure, the words "comprise," "including," "with," and "contain," and variations of these words, such as "comprising" and "includes" or similar terms, mean "including but not limited to" and are not intended to exclude (and do not exclude) other components. The use of any examples provided herein, or of formulations referring to examples ("for example," "such as," "for instance," and similar formulations), is intended solely to better illustrate the invention and does not indicate any limitation of the scope of the invention, unless otherwise claimed. No formulation in the description may be interpreted as construing an unclaimed element as essential for the implementation of the invention. All steps detailed in this description can be performed in any order or simultaneously, unless otherwise specified or the context requires otherwise. All aspects and / or features disclosed in this description may be combined in any combination, except for combinations in which at least some of these features and / or steps are mutually exclusive. As described herein, there may be certain combinations of aspects that offer a further advantage, such as the aspects of ion conductors for use in mass spectrometers and / or ion mobility spectrometers. In particular, the preferred features of the invention apply to all aspects of the invention and may be used in any combination. Likewise, features described in non-essential combinations may be used separately (not in combination). QUOTES INCLUDED IN THE DESCRIPTION This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited patent literature GB 2626803A [0002, 0023, 0026, 0042]GB 2617229A [0006, 0007]GB 2619766A

[0006] GB 2630325A

[0043] EP 3 410 463

[0060] US 9 136 101 [0066, 0069, 0083]US 9,536,722

[0067] US 10,699,888

[0072] GB 2,580,089

[0086] Cited non-patent literature A. Verenchikov et al., Journal of Applied Solution Chemistry and Modeling, 2017, 6, 1-22

[0087]

Claims

Amplifier arrangement for providing a varying electrode voltage for an ion-optical device, the amplifier arrangement comprising: a high-speed amplifier configured to receive an input signal at the amplifier arrangement and provide a low-voltage output signal; and a slowly adjustable voltage source arranged to float on the low-voltage output and configured to provide a high-voltage output signal to the amplifier arrangement; wherein the high-voltage output of the amplifier arrangement is fed back to control the high-speed amplifier. Amplifier arrangement according to claim 1, wherein the high-speed amplifier comprises a differential amplifier. Amplifier arrangement according to claim 2, wherein the differential amplifier is configured to receive the input signal to the amplifier arrangement at a first input and the high-voltage output signal of the amplifier arrangement at a second input. Amplifier arrangement according to one of the preceding claims, wherein the slowly adjustable voltage source is configured to be controlled by a control signal derived from the input signal at the amplifier arrangement and / or the low-voltage output signal of the high-speed amplifier. Amplifier arrangement according to claim 4, further comprising: a second amplifier configured to receive a signal based on the low-voltage output signal of the high-speed amplifier as an input signal and to generate the control signal based on the received signal. Amplifier arrangement according to claim 5, further comprising: a feedback amplifier configured to receive the low-voltage output signal of the high-speed amplifier as an input signal and to supply the signal based on the low-voltage output signal of the high-speed amplifier to the second amplifier. Amplifier arrangement according to claim 5 or claim 6, wherein the second amplifier is configured to receive the input signal at the amplifier arrangement which is adapted by the signal based on the low-voltage output signal of the high-speed amplifier. The amplifier arrangement according to one of the preceding claims, wherein the slowly adjustable voltage source comprises a galvanically isolated power supply. Amplifier arrangement according to one of the preceding claims, wherein the slowly adjustable voltage source comprises a voltage-controlled voltage source or a current source with a floating capacitor. Power supply for delivering at least one voltage to an electrode of an ion-optical device, comprising the amplifier arrangement of any one of the preceding claims. Ion analysis system comprising: ion-optical device, and power supply according to claim 10, configured to supply at least one voltage to an electrode of the ion-optical device. Ion analysis system according to claim 11, wherein the ion-optical device is a multipole mass filter or comprises one or more electrostatic lenses and / or deflectors. Ion analysis system according to claim 12, wherein the ion-optical device comprises a variable path length ion analyzer with an electrostatic lens and / or a deflector, wherein the power supply is configured to supply the electrostatic lens and / or the deflector with a voltage. Ion analysis system according to claim 13, wherein the voltage applied to the electrostatic lens and / or the deflector is selected between the following: a first voltage that causes ions to be injected into and / or extracted from the variable path ion analyzer; and a second voltage that causes a reversal of the drift velocity of the ions being analyzed by the variable path ion analyzer. Ion analysis system according to one of claims 11 to 14, wherein the ion optics device is part of a mass spectrometer. Ion analysis system according to claim 15, wherein the mass spectrometer is a time-of-flight mass spectrometer (TOF), a hybrid mass spectrometer or a Fourier transform mass spectrometer (FTMS).

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