Dual-frequency power supply system for mass spectrometry
By switching the RF frequency using a dual-frequency power supply system and combining low-frequency and high-frequency transformer components, the filtering problem of the mass spectrometer in different m/z ranges was solved, achieving high sensitivity and selective ion filtering over a wider range and improving the detection capability of the mass spectrometer.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- THERMO FINNIGAN LLC
- Filing Date
- 2024-10-11
- Publication Date
- 2026-05-12
AI Technical Summary
Existing mass spectrometers struggle to efficiently filter ions across different m/z ranges, especially in the lower m/z range, where the filtration performance is poor. Furthermore, conventional systems are limited in terms of power adjustment.
A dual-frequency power supply system is adopted, which drives the multi-pole electrode by switching the frequency of the RF generator. Combined with low-frequency and high-frequency transformer components, flexible filtering of different m/z ranges can be achieved.
It achieves high sensitivity and selective filtering over a wider mass-to-charge ratio range, especially for the effective detection of low mass-to-charge ratio ions, thus improving the detection capability of the mass spectrometer.
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Figure CN122029636A_ABST
Abstract
Description
[0001] Related applications This application claims priority to U.S. Provisional Patent Application No. 63 / 589,568, filed October 11, 2023, the contents of which are incorporated herein by reference in their entirety. Background of the Invention Mass spectrometers can be used to detect, identify, and / or quantify molecules based on the mass-to-charge ratio (m / z) of ions generated from molecules. A mass spectrometer typically includes an ion source for generating ions from molecules contained in a sample, a mass analyzer for separating ions based on their m / z, and an ion detector for detecting the separated ions. A mass spectrometer may include or be connected to a computer-based software platform that uses data from the ion detector to construct a mass spectrum showing the relative abundance of each ion among the detected ions as a function of m / z. Mass spectra can be used to detect and quantify molecules in simple and complex mixtures. In some configurations, separation systems such as liquid chromatography (LC), gas chromatography (GC), or capillary electrophoresis (CE) systems are coupled to a mass spectrometer in a combined system (e.g., LC-MS, GC-MS, or CE-MS system) to separate analytes from a sample before introducing them into the mass spectrometer.
[0003] One application of mass spectrometry is the identification, quantification, and structural determination of peptides, proteins, and related molecules in complex biological samples. In some such experiments, often referred to as multistage mass spectrometry (MSn, where n is 2 or greater) or tandem mass spectrometry (MS / MS or MS2 (n=2)), certain ions (called precursor ions) are isolated and fragmented in a controlled manner to produce product ions. The product ions are then subjected to mass analysis to generate a mass spectrum of the product ions. The mass spectrum of the product ions provides information that can be used to confirm the identification results, determine the quantity, and / or derive structural details about the analyte of interest.
[0004] Based on the different sizes of these molecules, mass spectrometers can filter for specific m / z ranges. However, due to the precision and magnitude of the input power characteristics utilized by the high-performance components of a mass spectrometer, configuring it to filter for all practical m / z ranges may be difficult. Summary of the Invention
[0005] The following description presents a simplified overview of one or more aspects of the methods and systems described herein to provide a basic understanding of such aspects. This invention is not a comprehensive review of all contemplated aspects, nor is it intended to identify key or decisive elements of all aspects, nor to define the scope of any or all aspects. Its sole purpose is to present, in a simplified form, some concepts of one or more aspects of the methods and systems described herein as a prelude to the more detailed description presented below.
[0006] In some exemplary examples, an apparatus for performing mass spectrometry analysis includes: a set of multipole electrodes; an RF generator configured to selectively output an RF voltage at a first resonant frequency or a second resonant frequency to drive the set of multipole electrodes; a low-frequency transformer assembly; a high-frequency transformer assembly; and a switching circuit configured to: connect the RF generator to the low-frequency transformer assembly when the RF generator outputs an RF voltage at the first resonant frequency, the low-frequency transformer assembly being configured to supply a first voltage to the output of the set of multipole electrodes based on the RF voltage; or connect the RF generator to the high-frequency transformer assembly when the RF generator outputs an RF voltage at the second resonant frequency, the high-frequency transformer assembly being configured to supply a second voltage to the output of the set of multipole electrodes based on the RF voltage.
[0007] In some exemplary examples, a dual-frequency power supply system for driving multipole electrodes includes: an RF generator configured to selectively output an RF voltage at a first resonant frequency or a second resonant frequency for driving the multipole electrodes; a low-frequency transformer assembly; a high-frequency transformer assembly; and a switching circuit configured to: connect the RF generator to the low-frequency transformer assembly when the RF generator outputs an RF voltage at the first resonant frequency, the low-frequency transformer assembly being configured to supply a first voltage to an output coupled to a set of multipole electrodes based on the RF voltage; or connect the RF generator to the high-frequency transformer assembly when the RF generator outputs an RF voltage at the second resonant frequency, the high-frequency transformer assembly being configured to supply a second voltage to an output coupled to a set of multipole electrodes based on the RF voltage.
[0008] In some exemplary examples, a method for controlling a dual-frequency power supply system to drive a multipole electrode includes: detecting a condition when the dual-frequency power supply system is operating in a first mode; and, based on the detected condition, switching the dual-frequency power supply system from operating in the first mode to operating in a second mode, the "switching" operation including: disconnecting the RF generator of the dual-frequency power supply system from a first transformer assembly configured to supply a first voltage to an output coupled to the multipole electrode based on the RF voltage when the RF generator outputs an RF voltage at a first resonant frequency; setting the RF generator of the dual-frequency power supply system to switch from outputting an RF voltage at the first resonant frequency to outputting an RF voltage at a second resonant frequency; and connecting the RF generator of the dual-frequency power supply system to a second transformer assembly configured to supply a second voltage to an output coupled to the multipole electrode based on the RF voltage. Attached Figure Description
[0009] The accompanying drawings illustrate various embodiments and are part of the specification. The illustrated embodiments are merely examples and do not limit the scope of this disclosure. Throughout the drawings, the same or similar reference numerals denote the same or similar elements.
[0010] Figure 1A An exemplary embodiment of a mass spectrometer including an ion accumulator is shown.
[0011] Figure 1B Another exemplary embodiment of a mass spectrometer including a capture-type mass analyzer is shown.
[0012] Figure 2 A functional diagram of an example mass spectrometry system is shown.
[0013] Figure 3 An exemplary implementation of a quality analyzer is shown.
[0014] Figure 4 An exemplary implementation of a power supply system for use as part of a quality analyzer is shown.
[0015] Figure 5 A functional diagram of an exemplary control system is shown.
[0016] Figure 6 An exemplary computing device is shown.
[0017] Figure 7 An exemplary method for controlling the power supply system used in a quality analyzer is shown. Detailed Implementation
[0018] This paper describes a dual-frequency power supply system for mass spectrometry analysis. The dual-frequency power supply system enables the mass spectrometer to operate in two different modes, filtering ions within different m / z ranges. These different m / z ranges may include not only higher and lower m / z ranges, but also m / z ranges of varying widths, allowing the mass spectrometer to filter at different m / z resolutions.
[0019] To achieve this feature, a dual-frequency power supply system may include a topology configured to switch the signal generator to drive one of two transformer circuits based on the frequency of the output signal generated by the signal generator. By connecting the signal generator to one transformer while disconnecting it from the other, the dual-frequency power supply system may be able to output power at two different frequencies, delivering optimal power to components of the mass spectrometer, such as the mass analyzer, multipole system, quadrupole filter, etc. Furthermore, a dual-frequency power supply system allows a single system to detect ions over a wider range of combined mass-to-charge ratios while still maintaining high sensitivity and selectivity (i.e., isolation width), particularly for ions with low mass-to-charge ratios.
[0020] As used in this article, "Th" or "Thomson" is a unit of mass-to-charge ratio equivalent to 1 Dalton (or atomic mass unit) per unit charge.
[0021] Various examples will now be described in more detail with reference to the accompanying drawings. The systems and methods described herein may provide one or more of the benefits described above, as well as various additional and / or alternative benefits that will become apparent herein.
[0022] The described dual-frequency power supply system can be utilized by any suitable mass spectrometer. Various specific implementations of the mass spectrometer will now be described. These implementations are merely illustrative, and other implementations of the mass spectrometer can be used in conjunction with the implementations described herein, such as liquid chromatography-mass spectrometry (LC-MS) systems, high-performance liquid chromatography-mass spectrometry (HPLC-MS) systems, gas chromatography-mass spectrometry (GC-MS) systems, or capillary electrophoresis-mass spectrometry (CE-MS) systems. The methods and systems described herein can also be operated with any other continuous flow sample source such as a flow injection mass spectrometry (FI-MS) system, in which the analyte is injected into the mobile phase (without separation in the column) and enters the mass spectrometer in a manner that varies in intensity over time (e.g., a Gaussian-like peak).
[0023] Figure 1A A functional diagram of a first exemplary embodiment 100A of a mass spectrometer 102 is shown. As shown, the mass spectrometer 102 includes an ion source 104, an ion accumulator 106, an m / z analyzer 108 (which analyzes ions based on their mass-to-charge ratio or m / z ratio, but is commonly referred to as mass analyzer 108), a detector 110, and a controller 112. The mass spectrometer 102 may also include any additional or alternative components (not shown) that may be suitable for a particular embodiment (e.g., ion optics, filters, ion storage devices, ion mobility analyzers, etc.).
[0024] Ion source 104 is configured to generate an ion stream 114 from components eluted by, for example, liquid chromatography and to deliver the ion stream 114 to ion accumulator 106. Ion source 104 may use any suitable ionization technique, including but not limited to electron ionization, chemical ionization, matrix-assisted laser desorption / ionization, electrospray ionization, atmospheric pressure chemical ionization, atmospheric pressure photoionization, inductively coupled plasma, etc. Ion source 104 may include various components for generating ions from components contained in a sample and delivering the ions to ion accumulator 106.
[0025] Ion accumulator 106 is a device configured to accumulate ions contained in ion stream 114 over an accumulation period. In some examples, ion accumulator 106 is an ion storage device configured to buffer downstream processes (such as mass analysis) to thereby improve scan speed and instrument sensitivity. In some examples, ion accumulator 106 is a beam-type device or trapping device, such as a multipole ion director (e.g., quadrupole ion director, hexapole ion director, octapole ion director, etc.), a linear quadrupole ion trap, a three-dimensional quadrupole ion trap, a cylindrical ion trap, a toroidal ion trap, an orbital electrostatic trap, a Kingdon trap, etc. Ion accumulation in ion accumulator 106 can be adjusted to achieve a target number of ions in ion accumulator 106. Adjustment of ion accumulation in ion accumulator 106 can be performed by a gate device (not shown) that transmits or blocks ion stream 114. The accumulated ions can then be transferred from ion accumulator 106 to mass analyzer 108 as ion stream 116.
[0026] Mass analyzer 108 is configured to isolate or separate ions in ion stream 116 based on the m / z of each ion in the ion stream, to filter ions and / or perform ion mass analysis, and frequently to provide ion stream 118 to detector 110. Mass analyzer 108 can be implemented by any suitable mass analyzer, including: multipole structures such as quadrupole mass filters, ion traps (e.g., linear quadrupole ion traps, three-dimensional quadrupole ion traps, cylindrical ion traps, toroidal ion traps, etc.), time-of-flight (TOF) mass analyzers, electrostatic trap mass analyzers (e.g., orbital electrostatic traps, such as orbital trap mass analyzers, Kingdon traps, etc.), Fourier transform ion cyclotron resonance (FT-ICR) mass analyzers, sector mass analyzers, etc. Although the term "quadrupole" is occasionally used herein as a descriptor for a quality analyzer structure, those skilled in the art will understand that the techniques, systems, and methods taught herein are not limited to specific implementations with a four-pole structure, and that other multipole structures (i.e., hexapole structures, octapole structures) may be used in conjunction with the techniques, systems, and methods taught.
[0027] In some examples, mass spectrometer 102 is a tandem mass spectrometer (time-tandem or spatial-tandem) configured to perform tandem mass spectrometry (e.g., MS / MS), or configured to perform multistage mass spectrometry (also referred to as MS). nThis can be a multistage mass spectrometer or a mixed mass spectrometer. For example, mass analyzer 108 may include multiple mass analyzers (m / z analyzers), mass filters (e.g., m / z filters), and / or collision cells. As used herein, the term "collision cell" may include any structure or device configured to generate product ions via a controlled dissociation process, ion neutralization, or ion-ion reaction process, and is not limited to devices for collision-activated dissociation. For example, a collision cell may be configured to fragment ions using collision-induced dissociation (CID), electron transfer dissociation (ETD), electron capture dissociation (ECD), photoinduced dissociation (PID), surface-induced dissociation (SID), etc. The collision cell may be positioned upstream of a mass filter that separates fragmented ions based on the ion's mass-to-charge ratio. In some embodiments, mass analyzer 108 may include a combination of multiple mass filters and / or collision cells, such as a triple quadrupole mass analyzer system, wherein the collision cell is inserted into the ion path between independently operable mass filters.
[0028] and Figure 1A Ion accumulator 106 is shown positioned upstream of mass analyzer 108. Ion accumulator 106 may be positioned at any other location within a tandem mass spectrometer or multistage mass spectrometer along the ion path from ion source 104 to detector 110 (e.g., between the first mass filter (Q1) and collision cell (Q2) and / or between collision cell (Q2) and second mass filter (Q3)). Additionally, mass spectrometer 102 may include more than one ion accumulator 106, such as when mass spectrometer 102 is a tandem mass spectrometer or multistage mass spectrometer.
[0029] Ion detector 110 is configured to detect ions in or from ion stream 118 within mass analyzer 108 at each of a variety of different m / z values, and in turn generate an electrical signal representing the ion intensity. The electrical signal is transmitted to controller 112 for processing, such as constructing a mass spectrum of the detected ions. For example, mass analyzer 108 may emit an emission beam of separated ions to detector 110, which is configured to detect ions in the emission beam and generate or provide data that can be used by controller 112 to construct a mass spectrum. Ion detector 110 can be implemented using any suitable detection device, including but not limited to electron multipliers, Faraday cups, etc.
[0030] The controller 112 is communicatively coupled to the mass spectrometer 102 and is configured to control various operations of the mass spectrometer. For example, the controller 112 may be configured to control the operation of various hardware components included in the ion source 104, ion accumulator 106, mass analyzer 108, and / or detector 110. For illustration, the controller 112 may be configured to control the accumulation time of the ion accumulator 106 and / or the mass analyzer 108, control the oscillating voltage power supply and / or DC power supply to supply RF voltage and / or DC voltage to the mass analyzer 108, adjust the values of the RF voltage and DC voltage to select the effective m / z (including the mass tolerance window) for analysis, and adjust the sensitivity of the ion detector 110 (e.g., by adjusting the detector gain).
[0031] Controller 112 may include any suitable hardware (e.g., processor, circuitry, etc.) and / or software that can serve a particular implementation. Although Figure 1A The controller 112 is shown to be included in the mass spectrometer 102; however, the controller 112 may alternatively be implemented in a manner that is completely or partially separate from the mass spectrometer 102, such as by means of a computing device communicatively coupled to the mass spectrometer 102 via a wired connection (e.g., cable) and / or a network (e.g., local area network, wireless network (e.g., Wi-Fi), wide area network, Internet, cellular data network, etc.). In some examples, the controller 112 may be implemented entirely or partially by the control module 256 (and vice versa).
[0032] Figure 1B A functional diagram of another exemplary embodiment 100B of the mass spectrometer 102 is shown. Embodiment 100B is similar to embodiment 100A, except that in embodiment 100B, the mass analyzer 108 is a trap-type mass analyzer and the ion accumulator 106 and the ion stream 116 from the ion accumulator 106 are omitted. Ions accumulate in the mass analyzer 108 during the accumulation time to reach the target ion quantity in the mass analyzer 108. In some embodiments, the mass spectrometer 102 may include an electrostatic trap mass analyzer / detector, such as an Orbitrap. ™ An analyzer that can combine the features of quality analyzer 108 and detector 110 into a single component or device.
[0033] Figure 2An example environment 200 in which the dual-frequency power supply system described herein may operate is illustrated. Specifically, environment 200 includes an example mass spectrometer system 204 for complex mass spectrometry experiments, and a computing device 206 configured to control the operation of mass spectrometer system 204 and / or perform post-processing on detector data generated from the mass spectrometer system. While this disclosure describes an environment including a mass spectrometer, in some embodiments, environment 200 may include different types of systems configured to manipulate and / or otherwise examine ions within an ion trap.
[0034] Figure 2 The mass spectrometer system 204 is shown as a hybrid mass spectrometer 210 including more than one type of mass analyzer. Specifically, the mass spectrometer 210 includes an ion trap mass analyzer 208 and an optional electrostatic trap mass analyzer 212 (e.g., ORBITRAP). ™ (Analyzer). However, it should be understood that different combinations of mass analyzers may be used for different applications, and therefore, the mass spectrometer system 204 may include fewer or more mass analyzers and / or different combinations of mass analyzers.
[0035] In operation of mass spectrometer 210, electrospray ionization source 214 provides ions from the sample to be analyzed to the orifice of heated ion transfer tube 216, where the ions enter the first vacuum chamber 218. Upon entry, the ions are captured and focused into a tight beam by ion collimation device 220 (e.g., stacked ring ion guide, ion lens, ion funnel, etc.). Mass spectrometer 210 is also shown to include a plurality of ion optical transfer elements 222 (e.g., optical transfer elements 222-1 to 222-4) configured to allow ions to pass between intermediate vacuum regions of the mass spectrometer during their journey. Mass spectrometer 210 is illustrated to include a curved beam guide 224 that separates most of the remaining neutral molecules and unwanted ion clusters (e.g., solvated ions, environmental contaminants, etc.) from the ion beam. For example, neutral molecules and ion clusters may follow a straight path, while the path of the ions of interest may be curved around a ninety-degree bend in the curved beam guide 224, thereby producing separation.
[0036] The RF (radio frequency) quadrupole mass filter 226 of the mass spectrometer 210 can be used as an adjustable mass filter to allow ions within a selected m / z range to pass through. Ion optical delivery components 222-2 deliver the m / z-filtered (m / z-selected) ions to a curved ion trap (“C-trap”) component 228. The C-trap 228 may be able to deliver ions along a path between the quadrupole mass filter 226 and the RF (radio frequency) ion trap mass analyzer 208. The C-trap 228 can also be configured to temporarily collect and store ion clusters. The C-trap 228 can then deliver ions as pulses or packets to the mass analyzer 212.
[0037] Figure 2 The multipole ion director 230 and optical transfer components 222-3 are also shown for guiding ions between the C-trap 228 and the ion trap mass analyzer 208. The multipole ion director 230 provides temporary ion storage capability, allowing ions generated in the first processing step of the analytical method to be retrieved later for processing in subsequent steps. The RF multipole ion director 230 can also be used as a fragmentation cell and ion trap (i.e., an ion routing multipole). Various ion optics along the path between the C-trap 228 and the ion trap mass analyzer 208 can be controllable, allowing ions to be transferred in either direction depending on the sequence of ion processing steps required in a particular analytical method.
[0038] Ion trap mass analyzer 208 Figure 2 The example is illustrated as including a dual-pressure region RF quadrupole linear ion trap 232 (e.g., a two-dimensional trap mass analyzer), which includes a high-pressure linear trap cell 234 and a low-pressure linear trap cell 236, the two cells being positioned adjacent to each other and separated by a plate lens with a small aperture that allows ions to pass between the two cells and also acts as a pumping limiter that allows different pressures to be maintained in the two traps.
[0039] The environment of high-pressure cell 234 is conducive to ion trapping, ion cooling, ion fragmentation via collision-induced dissociation or pulse-q dissociation, ion / ion reactions via electron transfer dissociation or proton transfer reactions, and some types of photoactivation, such as ultraviolet photodissociation (UVPD). The environment of low-pressure cell 236 is conducive to analytical scanning with high resolution and mass accuracy. Ion trap mass analyzer 208 is also shown to include ion detector 238 (e.g., a dual-polarity ion detector).
[0040] The use of electron transfer dissociation or proton transfer reactions within mass spectrometry leverages the ability to perform controlled ion-ion reactions within a mass spectrometer. Ion-ion reactions, in turn, utilize the ability to generate reagent ions and to mix reagent ions with sample ions. Mass spectrometer 210 is depicted as including a reagent ion source 240 disposed between a stacked ring ion director and a bent beam director 224. However, one or more additional reagent ion sources may be included in the example mass spectrometer system.
[0041] Figure 2 The example mass spectrometer 210 is also illustrated as including one or more additional components 242. Such additional components may include various combinations of one or more ion directors, ion traps, lenses, detectors, reagent ion sources, etc. Mass spectrometer 210 is merely an example configuration of a system capable of implementing / performing the systems and methods disclosed herein for dual m / z range filtering.
[0042] Environment 200 is also shown as including one or more computing devices 206. Figure 2 The computing device 206 depicted herein is merely illustrative and is not intended to limit the scope of this disclosure. The computing device 206 may include any combination of hardware or software capable of performing the indicated functions, including computers, network devices, Internet appliances, PDAs, wireless telephones, controllers, oscilloscopes, amplifiers, etc. The computing device 206 may also be connected to other devices not illustrated, or may be configured to operate as a stand-alone system.
[0043] Additionally, one or more computing devices in computing device 206 may be components of mass spectrometry system 204, devices separate from mass spectrometry system 204 and communicating with mass spectrometry system 204 via a network communication interface, or combinations thereof. For example, mass spectrometry system 204 may include a first computing device in computing device 206 that is a component of mass spectrometry system 204 and acts as a controller driving the operation of mass spectrometry system 204 (e.g., adjusting the scanning position on the sample by operating the scanning coil, controlling the dual-frequency power supply system, etc.). In this embodiment, mass spectrometry system 204 may also include a second computing device in computing device 206, such as a computer separate from mass spectrometry system 204, which can be executed to process detector data received from ion detector 238 to generate a spectral representation based on the detector data (e.g., chromatograms, extracted ion current (EIC) distribution, etc.), and / or to perform other types of analysis or post-processing of the detector data. The computing device 206 can also be configured to receive user selections via a keyboard, mouse, touchpad, touchscreen, wireless device, or other user interface.
[0044] Additionally, computing device 206 may be configured to control mass spectrometry system 204 to allow mass spectrometry analysis of a sample. For example, one or more user selections, automation programs, or combinations thereof may allow computing device 206 to cause mass spectrometry system 204 and / or its components to perform any of the methods described in this disclosure and use any of the parameters described herein. User selections, automation programs, or combinations thereof may then cause computing device 206 to generate and / or analyze sample-related detector data from mass spectrometry system 204, and / or create one or more chromatograms associated with the mass spectrometry analysis performed on the sample.
[0045] Figure 2The document also includes schematic diagrams of an example computing architecture 250 illustrating computing device 206. Example computing architecture 250 illustrates additional details of software and hardware components that can be used to implement one or more of the technologies described herein. Computing architecture 250 may be implemented in a single computing device 206 or across multiple computing devices 206. For example, the various modules and / or data constructs depicted in computing architecture 250 may be executed by different computing devices 206 and / or stored on different computing devices. In this way, different process steps of the methods disclosed herein may be executed and / or implemented by separate computing devices 206 and in various sequences within the scope of this disclosure. In other words, in some specific embodiments, the functionality provided by the illustrated components may be combined in fewer components or distributed across additional components. Similarly, in some specific embodiments, the functionality of some illustrated components may not be provided and / or other additional functionality may be used.
[0046] In computing architecture 250, the computing device includes one or more processors 252 and memory 254 communicatively coupled to the one or more processors 252. While not intended to be limiting, computing architecture 250 is shown as including a control module 256 stored in memory 254. As used herein, the term "module" is intended to indicate an example portion of executable instructions for discussion purposes and not to indicate any type of requirement or required method, manner, or organization. Thus, while various "modules" are described, their functionality and / or similar functionality may be arranged in different ways (e.g., combined into a smaller number of modules, decomposed into a large number of modules, etc.). Furthermore, while specific functions and modules are described herein as being implemented by software and / or firmware executable on a processor, in other cases, any one or all of the modules may be implemented wholly or partially by hardware (e.g., dedicated processing units, etc.) to perform the described functions. As discussed above in various specific embodiments, the modules described herein in association with computing architecture 250 may execute across multiple computing devices 206.
[0047] Control module 256 may be executed by processor 252 to cause computing device 206 and / or mass spectrometer system 204 to take one or more actions and / or perform system functions or maintenance. In some embodiments, control module 256 may cause mass spectrometer system 204 to perform mass spectrometry analysis on a sample. More specifically, according to this disclosure, control module 256 may be able to be executed to cause mass spectrometer system 204 and / or its components to perform any of the methods described in this disclosure and use any of the parameters described herein.
[0048] As discussed above, computing device 206 includes one or more processors 252 configured to execute instructions, applications, or programs stored in memory 254 accessible to the one or more processors 252. In some examples, the one or more processors 252 may include hardware processors, including but not limited to hardware central processing unit (CPU), graphics processing unit (GPU), etc. While in many cases these technologies are described herein as being executed by one or more processors 252, in some cases these technologies are implemented by one or more hardware logic components, such as field-programmable gate arrays (FPGAs), complex programmable logic devices (CPLDs), application-specific integrated circuits (ASICs), system-on-a-chip (SoCs), or combinations thereof.
[0049] Memory 254 accessible by one or more processors 252 is an example of a computer-readable medium. Computer-readable media can include two types: computer storage media and communication media. Computer storage media can include volatile and non-volatile, removable and non-removable media implemented in any method or technology for storing information such as computer-readable instructions, data structures, program modules, or other data. Computer storage media includes, but is not limited to, random access memory (RAM), read-only memory (ROM), erasable programmable read-only memory (EEPROM), flash memory or other storage technologies, optical disc read-only memory (CD-ROM), digital universal disk (DVD) or other optical storage devices, magnetic tape cassettes, magnetic tape, disk storage devices or other magnetic storage devices, or any other non-transfer medium that can be used to store desired information and is accessible by a computing device. Generally, computer storage media can include computer-executable instructions that, when executed by one or more processing units, cause the various functions and / or operations described herein to be performed. In contrast, communication media embody computer-readable instructions, data structures, program modules, or other data in modulated data signals (such as carrier waves) or other transmission mechanisms. As defined herein, computer storage media does not include communication media. Those skilled in the art will also understand that, for memory management and data integrity purposes, items or portions thereof may be transferred between memory 254 and other storage devices. Alternatively, in some embodiments, some or all of the software components may be executed in memory on another device and communicate with computing device 206. Some or all of the system components or data structures may also be stored (e.g., as instructions or structured data) on a non-transitory computer-accessible medium or portable article of manufacture for retrieval by a suitable driver, various examples of which are described above. In some embodiments, instructions stored on a computer-accessible medium separate from computing device 206 may be transmitted to computing device 206 via a transmission medium or signal (such as electronic, electromagnetic, or digital signals transmitted via a communication medium such as a wireless link). Various embodiments may further include receiving, transmitting, or storing instructions and / or data implemented on a computer-accessible medium as described above.
[0050] Control module 256 and / or controller 112 may also include and / or provide a user interface configured to enable a user to interact with mass spectrometer system 204 and / or mass spectrometer 102. The user may interact with control module 256 and / or controller 112 via the user interface through tactile, visual, auditory, and / or other sensory communication. For example, the user interface may include a display device (e.g., liquid crystal display (LCD) screen, touchscreen, etc.) for displaying information (e.g., mass spectra, notifications, etc.) to the user. The user interface may also include an input device (e.g., keyboard, mouse, touchscreen device, etc.) that allows the user to provide input to control module 256 and / or controller 112. In other examples, the display device and / or input device may be decoupled from control module 256 and / or controller 112, but communicatively coupled to it. For example, display devices and input devices may be included in a computer (e.g., a desktop computer, laptop computer, etc.) that is communicatively connected to the control module 256 and / or the controller 112 via a wired connection (e.g., via one or more cables) and / or a wireless connection.
[0051] Control module 256 and / or controller 112 acquire data acquired over time by mass spectrometry system 204 and / or mass spectrometer 102. This data may include a series of mass spectra comprising intensity values of ions produced by analytes in the sample, these intensity values varying with the m / z of the ions. This series of mass spectra may be represented in a three-dimensional plot, where time (e.g., retention time) is plotted along the X-axis, m / z along the Y-axis, and intensity along the Z-axis. Spectral features on the plot (e.g., Z-axis peaks of intensity) represent the detection of ions produced from various analytes contained in the sample by mass spectrometry system 204 and / or mass spectrometer 102. The X and Z axes of the plot may be used to generate elution curves (e.g., mass chromatograms) plotting the detection intensity as a function of time at a selected m / z.
[0052] In mass spectrometry analysis, the m / z range for selecting the RF quadrupole mass filter (which enables the mass analyzer and / or other components within the mass spectrometer) depends on the operating frequency f and the maximum magnitude (2V) of the RF voltage that can be applied between the x and y rod electrode pairs of the quadrupole mass filter. 0-peak, max The quadrupole electrode assembly's characteristic dimension r0 is also considered. For example, in some embodiments, the maximum mass-to-charge ratio (m / z) of the quadrupole m / z filter is determined when the RF voltage varies sinusoidally. max It can be roughly determined by the following expression: ; in Coulombs / elementary charge kilograms (kg) / Daltons (Da) The upper limit of m / z (mass to elementary charge ratio) corresponding to the m / z selection of the quadrupole mass filter. This indicates the operating frequency of the quadrupole in kilohertz (kHz), and The quadrupole feature dimensions are described in millimeters (mm). In the example embodiment, the r0 of the quadrupole m / z filter electrode (the round rod electrode is ground into a hyperbolic profile) assembly is in the range of 4 mm to 6 mm.
[0053] In conventional systems, the initial design of the instrument specifies the values of r0 (component size) and f, which are not easily changed after machine production due to mechanical or electronic constraints, as well as design goals for selecting the resolution achievable in m / z and the efficiency of ion transport through the device when operating near the maximum achievable resolution and at the upper limit of its m / z range. For example, regarding... Figure 2 The modern high-performance mass spectrometer systems described and depicted have a 2Vo-peak,max value of approximately 10,000 volts at an operating frequency of approximately 1100 kHz. To generate such a large voltage without consuming excessive power, a tuned circuit voltage transformer network is used. These cases involve custom-made (typically air-core) inductors capable of dissipating over 100 watts. The most widely used specific implementations routinely involve large, machined circuit transformer inductor assemblies (e.g., a few turns primary and tens of turns secondary) connected across electrode pairs (capacitive loads) of an m / z filter or quadrupole linear ion trap. When driven at the configured resonant frequency, a large voltage can be applied to the electrodes of the m / z analyzer. For example, RF amplifier circuitry and other electronics are selected and tuned to operate optimally at the design frequency. If operated at different frequencies, resonant coupling will decrease, and unwanted Joule heating may occur. Therefore, in operation, conventional systems can successfully manipulate ions within a predetermined mass-to-charge ratio range as determined by the above equations, and the key to obtaining a specific mass-to-charge ratio lies in adjusting the applied voltage (2Vo-peak). In the case of an m / z filter, a similarly applied DC voltage can be adjusted to obtain a specific m / z ratio.
[0054] To obtain a higher (m / z) max The value can be increased to increase the maximum applied voltage. However, the maximum RF voltage value can be limited by various factors, such as voltage breakdown across the insulators that separate the rod electrodes from each other and other conductive surfaces, or voltage breakdown across the wires that deliver the voltage to or within the feedthroughs that deliver the RF voltage to the vacuum chamber. The operating pressure of a quadrupole m / z filter may often be too low to generate an arc, but breakdown across and sometimes through the insulators can occur, causing permanent damage to the device.
[0055] Additionally or alternatively, the maximum RF voltage may be limited by field emissions induced by high electric fields generated by applying a high RF voltage to the rod electrodes of the quadrupole m / z filter. Emissions may originate from the rod electrodes or other nearby counter electrodes. Typically, field emissions are not destructive, but they can cause interference with ion signals (noise) and other problems.
[0056] Additionally or alternatively, the maximum RF voltage may be limited by high-voltage breakdown, arcing, or discharge on the atmospheric side of the tuning RF transformer circuitry (coils, capacitors, insulators, etc.), electrical connections, or one or more vacuum feedthroughs that deliver high-voltage RF to the vacuum chamber containing the quadrupole m / z filter electrodes. Such breakdown can damage the device. Even a very small discharge is often sufficient to interfere with adjusting the applied RF voltage to the very high precision required for proper operation of the RF quadrupole m / z analyzer.
[0057] Additionally or alternatively, depending on the size of the instrument and / or the instrument's power budget, there may be practical constraints on the size and power output of the RF power amplifier driving the RF transformer. Because there can be fairly extreme accuracy and drift requirements during the adjustment of the magnitude of the RF voltage applied to the rod electrodes, the RF amplifier driving the RF transformer may require relatively low distortion. For example, a usable AB-type amplifier typically has an efficiency of 60% (or less) when converting input power to output RF power. In one example, for a RF quadrupole m / z filter analyzer operating at a nominal frequency of 1100 kHz with a maximum selected m / z of 2000 Th, approximately 150 W of RF can be delivered to the primary of the transformer coil. Resistive losses in the transformer coil account for a significant portion of this power consumption. Additional losses may result from resistive losses from eddy currents induced in the conductive aluminum housing encapsulating the RF transformer circuitry, as well as from RF absorption by various materials used throughout the assembly (e.g., adhesives, plastics, printed circuit board materials for the coil tubes and connectors, etc.). In some implementations, Litz wire can be used to reduce resistive losses in the transformer coil, and fan-driven forced convection cooling can be used to prevent overheating of the transformer coil and the entire assembly. Resistive losses typically increase with frequency, therefore, for a given electrode configuration (fixed capacitance, fixed r0), to achieve the same... The required RF power may increase with frequency, for example, by more than f. 4 The relationship, which can be expected to derive from the quadratic relationship between voltage and power and the relationship provided above, is... The expression.
[0058] Therefore, for a variety of reasons, simply increasing the maximum value of the applied RF voltage is generally impractical. As an alternative, reducing the operating frequency can be considered to achieve a greater... Value. For a given maximum voltage that can be applied between the x and y bar electrode pairs, reducing the RF frequency increases the upper limit of the m / z selection, as described in the equation above. However, reducing the operating frequency may reduce the efficiency of ion transport through the device and generally reduces the device's actual maximum resolution. For m / z filters, reducing the operating frequency increases the actual minimum m / z transport bandwidth (i.e., isolation width) centered at a given m / z. For example, the isolation width of a multipole (e.g., an RF quadrupole m / z filter) can be as small as 0.4Th to 1Th when operating at high frequencies, but as large as 10Th to 100Th when operating at sufficiently reduced frequencies. Therefore, RF quadrupole m / z filters can generally exhibit lower ion transport rates (and thus lower instrument sensitivity) within the m / z transport band, causing a stronger dependence of ion transport on kinetic energy and introducing general irregularities in ion transport within the m / z transport band.
[0059] In practice, reducing the operating frequency of a quadrupole filter can lead to a poorer m / z peak (line) shape, a poorer actual minimum peak width, and a degraded m / z peak shape. Furthermore, the resolution of the ion (axial) velocity distribution may decrease (the minimum m / z transmission window width widens). Therefore, when isolating ions with low m / z values (which have high velocities for a given kinetic energy / charge), it is designed to operate only at low frequencies to obtain very high (m / z) values. max The system may have unacceptable resolution. As described above, simply extending the maximum RF voltage and power is insufficient. Alternative solutions may often be impractical because the system may be designed with power and RF voltage limitations and margins.
[0060] To address these issues, the systems and methods described herein may include multipole electrode structures (e.g., quadrupole electric field application structures) and dual-frequency power supply systems (e.g., dual-frequency RF generation systems) configured to operate at two different frequencies and thus have two distinct m / z operating ranges. The dual-frequency RF generation system may include two transformer circuits (e.g., coil assemblies) and a switching circuit configured such that the system drives one of the two transformers according to the operating frequency range while decoupling the other. This configuration allows for rapid switching between filtering for two different m / z ranges, where component design for input impedance is easier, resulting in optimal power delivery from the RF amplifier. The systems and methods taught herein enable users to effectively m / z filter ions with high m / z values (e.g., in the range of 2000Th to 8000Th) while maintaining high resolution when filtering ions with lower m / z values (e.g., in the range of 50 to 2000Th) using the same m / z analyzer.
[0061] Figure 3 An example configuration 300 of a multipole structure is shown, which may be part of a quality analyzer and an associated dual-frequency power supply system 308. Specifically, configuration 300 shows a quadrupole electrode structure with a set of electrodes 302, including x-bar electrode pairs 304 (e.g., x-bar electrodes 304-1 and 304-2) and y-bar electrode pairs 306 (e.g., y-bar electrodes 306-1 and 306-2) coupled to the dual-frequency power supply system 308. The dual-frequency power supply system 308 may include an x-bar DC source 310 coupled to and driving the x-bar electrode pairs 304. The dual-frequency power supply system 308 may also include a y-bar DC source 312 coupled to and driving the y-bar electrode pairs 306. The dual-frequency power supply system 308 also includes an RF amplifier 314 configured to output a high-power RF voltage at a first frequency or a second frequency to a relatively low impedance load (e.g., 75 ohms) depending on the operating mode of the quality analyzer, thereby enabling the quality analyzer to filter out ions in a first m / z range or a second m / z range, respectively. The RF amplifier 314 can output a signal voltage to a switching circuit 316.
[0062] The switching circuit 316 can be configured to connect the RF amplifier 314 to one of two transformer components in a single dual-resonant frequency LC network to output a transformed high RF voltage within one of the two resonant frequency bands, depending on the operating mode. For example, in a low-frequency operating mode, the switching circuit 316 can connect the RF amplifier 314 to a low-frequency transformer component 318 (which may include a primary winding 320 and a secondary winding 322, the secondary winding being implemented as a split winding including an x-bar secondary winding 322-1 and a y-bar secondary winding 322-2, such as...). Figure 3 (As shown), and the RF amplifier 314 is connected to the high-frequency transformer assembly 324 (which may include a primary winding 326 and a secondary winding 328, the secondary winding being implemented as a split winding including an x-bar secondary winding 328-1 and a y-bar secondary winding 328-2, as shown). Figure 3 (As shown) Disconnect. Conversely, in high-frequency operation mode, switching circuit 316 can connect RF amplifier 314 to high-frequency transformer assembly 324 and disconnect RF amplifier 314 from low-frequency transformer assembly 318. In this way, either low-frequency transformer assembly 318 or high-frequency transformer assembly 324 can be driven by RF amplifier 314 with most of the RF drive voltage to provide low-frequency or high-frequency signals to the quadrupole for the high m / z filtering range or low m / z filtering range, respectively.
[0063] For example, to operate an m / z analyzer with a high or "extended" m / z range, the RF amplifier 314 outputs an RF voltage with a frequency in the lower of the two resonant bands of the transformer network. In some examples, the low-frequency RF voltage may be in the range of 250 kHz to 750 kHz, or approximately 500 kHz. A switching circuit 316 connects the RF amplifier 314 to the primary winding 320 of the low-frequency transformer assembly 318 while disconnecting it from the primary winding 326 of the high-frequency transformer assembly 324. Thus, the low-frequency transformer assembly 318 and the low-frequency resonant capacitor 330 connected to the two halves of the secondary winding 322 act as the main resonant elements to supply the larger portion of the boosted RF voltage used to drive the quadrupole electrodes, where a smaller, but not insignificant, portion of this boosted voltage originates from the inductance of the secondary winding 328 of the high-frequency transformer assembly 324. Connecting the RF amplifier only to the primary winding 320 of the low-frequency transformer assembly 318 typically allows for a more direct design of the impedance matching network circuitry within the primary winding 320 and primary winding 326, as well as the switching circuit 316. To obtain the maximum RF voltage across the x-bar and y-bar electrodes with the minimum power output within the maximum power output available from the RF amplifier 314, the RF amplifier 314 is driven at an output frequency very close to (equal to or very close to) the lower resonant frequency of the voltage conversion network, ensuring proper impedance matching (and optionally, conversion) in the transmission of RF power from the output of the RF amplifier 314 to the primary winding 320 of the transformer assembly. The network elements of the entire LC network (including: the inductance of both the secondary winding 322 of the low-frequency transformer assembly 318 and the secondary winding 328 of the high-frequency transformer assembly 324; the low-frequency resonant capacitor 330; the capacitance of a set of electrodes 302; any other capacitance introduced by the placement of electrical feedthroughs, electrical connectors, etc. at the ends of the x-bar electrode 304 and y-bar electrode 306; any other added capacitance; and the x-bar and y-bar electrode blocking capacitor 332) are all combined to determine the lower resonant frequency (the center frequency of the narrow lower resonant band) and the higher resonant frequency (the center frequency of the narrow high-frequency resonance) of the network.
[0064] Conversely, to operate the quadrupole m / z analyzer with a lower m / z range (and higher m / z resolution and ion transport rate), the RF amplifier 314 can output a high-frequency RF voltage (e.g., an RF voltage above a threshold frequency and / or below a low-frequency RF voltage). In some examples, the frequency of the high-frequency RF voltage can be in the range of 800 kHz to 1400 kHz, or approximately 1100 kHz. A switching circuit 316 connects the RF amplifier 314 to the primary winding 326 of the high-frequency transformer assembly 324 while disconnecting the RF amplifier 314 from the primary winding 320 of the low-frequency transformer assembly 318. Therefore, the high-frequency transformer assembly 324 and the quadrupole load (which can be used as a capacitor in the circuit) can act as the main resonant circuit to supply the high-frequency converted voltage, where the influence from the low-frequency transformer assembly 318 is minimal, which, together with the low-frequency resonant capacitor 330, can operate somewhat like a short circuit at the high-frequency RF voltage. Therefore, this also allows impedance matching to be easier to drive the primary winding 326 of the high-frequency transformer assembly 324 at or near the high-frequency resonance of the transformer network.
[0065] For example, in ion m / z filtration applications, the high and low m / z ranges can be any suitable m / z range. Depending on the m / z range, a suitable frequency range can be determined for the RF voltage and other parameters of the dual-frequency power supply system 308, such as the primary and secondary turns, the secondary inductance, and / or other physical parameters of the low-frequency transformer assembly 318 and the high-frequency transformer assembly 324. For example, the low m / z range (higher frequency operating mode) of the m / z filter can be approximately 50Th to 2000Th, which is suitable for experiments involving small molecules and / or peptides. In some examples, when the system operates in the lower m / z range, the m / z selection width can be set in the range of 0.4Th to 1500Th. The high m / z range (lower RF frequency) operating mode allows for extending the m / z range for m / z selection to approximately 2000Th to 8000Th, which is suitable for experiments involving proteins and / or protein complexes ionized to this m / z range. In some examples, when the system operates in an extended m / z range mode (low RF frequency mode), the m / z selectivity width can be selected to be a value ranging from 5Th to 3000Th. Low m / z range modes (higher frequency modes) typically allow for higher m / z selectivity (filtering) resolution for ions, while high m / z ranges allow for higher m / z magnitude values. Therefore, a high-frequency RF voltage can be any suitable m / z range with a lower lower limit (e.g., 50Th) than the lower limit of the m / z range achieved by a low-frequency RF voltage (e.g., 2000Th as an example). Additionally or alternatively, a high-frequency RF voltage can be selected to allow for an m / z range that enables the mass analyzer to filter ions beyond a threshold m / z resolution level, while a low-frequency RF voltage can be selected to allow for an m / z range beyond a threshold m / z magnitude level. Advantages of high-frequency modes can include higher maximum resolution (i.e., narrower minimum achievable m / z peak width than in other modes), higher ion transport rates at a given resolution, and lower sensitivity of m / z peak shape or resolution to ion velocity. The advantages of low-frequency mode may include a larger maximum m / z value for selection.
[0066] In some examples, the frequency of the low-frequency RF voltage can be set to be less than half the frequency of the high-frequency RF voltage. For example, the frequency of the low-frequency RF voltage can be a predetermined amount less than half the frequency of the high-frequency RF voltage (e.g., 40 kHz) to avoid problems caused by harmonic components in the RF voltage.
[0067] Furthermore, in some examples, the dual-frequency power system 308 may include additional components and / or features to eliminate harmonic signal components. For example, the low-frequency transformer assembly 318 and / or the high-frequency transformer assembly 324 may be implemented by or include air-core transformers to reduce or eliminate the generation of harmonic RF voltage components. Additionally, the air-core transformer may reduce or minimize power losses that may occur due to the nonlinearity of the magnetic properties of the core material.
[0068] Additionally or alternatively, the dual-frequency power system 308 may also include additional filtering components in or coupled to the switching circuit 316. For example, Figure 4 An example configuration 400 is shown, illustrating components of a switching circuit 316, with some components of configuration 300 also shown for context. As in configuration 300, an RF amplifier 314 is coupled to the switching circuit 316, and the switching circuit 316 switches the coupling of the RF amplifier 314 between the primary winding 320 of a low-frequency transformer assembly 318 and the primary winding 326 of a high-frequency transformer assembly 324. As shown, the switching circuit 316 may include a pair of low-pass filters (e.g., low-pass filter 404 and low-pass filter 406). Low-pass filters 404 and 406 can be implemented in any suitable manner, such as a passive low-pass dual-π network type LC filter.
[0069] The switching circuit 316 may include two branches 402, branch 402-1 leading to the low-frequency transformer assembly 318 and branch 402-2 leading to the high-frequency transformer assembly 324. Each branch 402 may include two switching mechanisms with a low-pass filter between them. For example, branch 402-1 may include switches 408 (e.g., switches 408-1 and 408-2) coupled to the low-pass filter 404. Similarly, branch 402-2 may include switches 410 (e.g., switches 410-1 and 410-2) coupled to the low-pass filter 406.
[0070] When the quadrupole filter operates at a lower resonant frequency, the low-pass filter 404, connected in series between switches 408, provides virtually complete transmission of RF power at the fundamental frequency and provides progressively stronger attenuation of second-, third-, and higher-order harmonics in the path to the primary winding 320 of the low-frequency transformer assembly 318. Furthermore, as described above, switch 410 can be disconnected to disconnect the RF amplifier 314 from the high-frequency transformer assembly 324.
[0071] Conversely, when the quadrupole filter operates at a higher resonant frequency, the low-pass filter 406 connected in series between switches 410 can provide virtually complete transmission of RF power at the (higher) fundamental frequency and provides progressively greater attenuation of second-, third-, and higher-order harmonics in the path to the primary winding 326 of the high-frequency transformer assembly 324. Similarly, switch 408 can be turned off to disconnect the RF amplifier 314 from the low-frequency transformer assembly 318.
[0072] Additionally, low-pass filters 404 and / or 406 may also provide impedance transformation functionality. For example, RF amplifier 314 may be designed to drive a 50-ohm resistive load. Low-pass filters 404 and 406 provide impedance transformation from 50 ohms to 75 ohms to allow RF power to be transmitted through a 75-ohm coaxial cable to the primary windings 320 and 326, which have an input impedance of 75 ohms, when driven at lower and higher resonant frequencies, respectively.
[0073] Additionally or alternatively, the dual-frequency power supply system 308 may include one or more RF detector capacitors 412. The RF detector capacitors may sample an RF current, which is rectified in the RF control circuitry 414 to provide high-precision and stable feedback for adjusting the RF magnitude applied to the quadrupole electrodes. An error signal (modulation) representing the difference between the detected RF magnitude and the command RF magnitude setting signal may be transmitted from the RF control circuitry 414 to the RF amplifier. This error signal may be full-wave modulated onto a reference RF sine wave generated in a programmable RF generator 416, which may be configured to output the reference RF sine wave to the RF amplifier 314. The modulated RF voltage may be amplified by the RF amplifier 314 and used to drive either the low-frequency transformer assembly 318 or the high-frequency transformer assembly 324.
[0074] Additionally or alternatively, the RF control circuit 414 may provide a signal derived from the magnitude of the detected RF amplitude, which may be transmitted to a DC rod driver amplifier module that generates differential DC voltages to provide m / z selection in the quadrupole. These DC voltages may be further filtered by an RF blocking filter (not shown) and injected at the center tap of the low-frequency transformer assembly 318. Furthermore, the value of the capacitor 332 across the outputs of the x-rod DC source 310 and the y-rod DC source 312 may be selected such that the capacitance of the capacitor 332 produces a sufficiently low impedance that a suitably small portion of the RF voltage at either output of the secondary winding 322 of the low-frequency transformer assembly 318 appears across the capacitor 332.
[0075] The switching circuit 316 can provide relatively fast switching between quadrupole operating frequencies (e.g., approximately ten milliseconds or less). For example, the dual-frequency power system 308 may include and / or communicatively coupled to a controller (e.g., control module 256, controller 112, and / or any other suitable controller) connected to and / or communicating with the RF generator 416, and configured to selectively operate in different operating modes corresponding to the operating frequencies. The controller may configure the RF generator 416 to output a low frequency or a high frequency (e.g., via RF amplifier 314), and configure the switching circuit 316 to connect the RF amplifier 314 to either the low-frequency transformer assembly 318 or the high-frequency transformer assembly 324 accordingly.
[0076] When switching between operating frequencies, the output of RF amplifier 314 can be made zero by turning off the RF frequency reference signal. The RF voltage on the connected transformer circuit is allowed to attenuate sufficiently to switch the switch of switching circuit 316, and then RF amplifier 314 can be re-energized by outputting a new operating frequency from RF generator 416. The RF voltage delivered to the quadrupole m / z filter rod electrodes and the DC rod electrode voltage can be balanced to appropriate values to allow the desired m / z ions to be transmitted with the desired m / z resolution (transmission window width).
[0077] The advantage of the system and method taught in this paper is that it enables rapid switching between high-frequency and low-frequency modes without the need for expensive high-voltage power supplies and electronic relay switches to switch taps on the output coils of a single transformer power supply system. By employing switching circuit 316 and two tuning transformer assemblies, switching circuit 316 can utilize a lower-cost RF-compatible relay switch designed to handle maximum voltages of approximately several hundred volts, as well as a lower-cost RF generator.
[0078] In some examples, the controller (e.g., controller 112, computing device 206, etc.) may be configured to switch operating modes based on detected conditions. For example, detected conditions may include user-provided input indicating the selected operating mode. Additionally or alternatively, the controller, mass analyzer, and / or mass spectrometer may be configured to determine the operating mode, for example, based on the detection of ions in a specific m / z range (e.g., based on the detection of ions in the m / z range of the current operating mode, based on scans across two operating modes, etc.) and / or the absence of detected ions in a specific m / z range (e.g., switching modes based on the detection of ions below a threshold level in the current operating mode). Additionally or alternatively, the controller, mass analyzer, and / or mass spectrometer may determine the operating mode based on any other suitable conditions that provide an indication of the m / z range of the desired ion.
[0079] One or more operations associated with the dual-frequency system used for mass spectrometry analysis may be performed by a control system in conjunction with an MS system (e.g., mass spectrometer 102, mass spectrometer system 204, LC-MS system, GC-MS system, or CE-MS system). The control system may control and / or perform one or more operations described herein. Figure 5 A functional diagram of an exemplary control system 500 (“System 500”) is shown. System 500 may be implemented wholly or partially by an MS system (such as mass spectrometer 102 or mass spectrometer system 204 (e.g., by control module 256 and / or controller 112)). Alternatively, System 500 may be implemented separately from the MS system (e.g., a remote computing system or server that is decoupled from but communicatively coupled to control module 256 and / or controller 112).
[0080] System 500 may include, but is not limited to, a memory 502 and a processor 504 that are selectively and communicatively coupled to each other. The memory 502 and the processor 504 may each include or be implemented with hardware and / or software components (e.g., a processor, memory, communication interface, instructions stored in memory for execution by the processor, etc.). The memory 502 and the processor 504 may be distributed among multiple devices and / or multiple locations that can serve a particular specific implementation.
[0081] Memory 502 may hold (e.g., store) executable data that processor 504 uses to perform any of the operations described herein. For example, memory 502 may store instructions 506 that can be executed by processor 504 to perform any of the operations described herein. Instructions 506 may be implemented by any suitable application, software, code, and / or other instance of executable data. Memory 502 may also hold any data acquired, received, generated, managed, used, and / or transmitted by processor 504.
[0082] Processor 504 is configured to execute (e.g., execute instructions 506 stored in memory 502 to perform) the various processing operations described herein. It will be appreciated that the operations and examples described herein are merely illustrative of many different types of operations that can be performed by processor 504. Any reference to operations performed by system 500 in this description is to be understood as being performed by processor 504 of system 500. Furthermore, any operation performed by system 500 in this description can be understood to include system 500 booting, commanding, or instructing another system or device to perform an operation.
[0083] In some embodiments, one or more of the systems, components, and / or processes described herein may be implemented and / or performed by one or more suitably configured computing devices. To this end, one or more of the systems and / or components described above may include, or be implemented by, any computer hardware and / or computer implementation instructions (e.g., software) embodied on, or implemented by, at least one non-transitory computer-readable medium configured to perform one or more of the processes described herein. Specifically, system components may be implemented on one physical computing device or on more than one physical computing device. Therefore, system components may include any number of computing devices and may employ any number of computer operating systems.
[0084] In some embodiments, one or more processes described herein may be implemented at least in part as instructions embodied in a non-transitory computer-readable medium and executable by one or more computing devices. Typically, a processor (e.g., a microprocessor) receives instructions from a non-transitory computer-readable medium (e.g., memory, etc.) and executes those instructions, thereby performing one or more processes, including one or more processes described herein. Such instructions may be stored and / or transmitted using any of a variety of known computer-readable media.
[0085] Computer-readable media (also known as processor-readable media) include any non-transitory medium that participates in providing data (e.g., instructions) that can be read by a computer (e.g., by the computer's processor). Such media can take many forms, including but not limited to non-volatile and / or volatile media. Non-volatile media may include, for example, optical discs or magnetic disks, and other permanent storage. Volatile media may include, for example, dynamic random access memory (“DRAM”), which typically constitutes main memory. Common forms of computer-readable media include, for example, magnetic disks, hard disks, magnetic tapes, any other magnetic media, optical disc read-only memory (“CD-ROM”), digital video discs (“DVD”), any other optical media, random access memory (“RAM”), programmable read-only memory (“PROM”), electrically erasable programmable read-only memory (“EPROM”), FLASH-EEPROM, any other memory chip or cassette disk, or any other tangible medium that is computer-readable.
[0086] Figure 6 An exemplary computing device 600 is shown, which can be specifically configured to perform one or more processes described herein. Figure 6 As shown, computing device 600 may include a communication interface 602, a processor 604, a storage device 606, and an input / output (“I / O”) module 608 that are communicatively connected to each other via communication infrastructure 610. Although Figure 6An exemplary computing device 600 is shown, but Figure 6 The components illustrated are not intended to be limiting. Additional or alternative components may be used in other embodiments. A more detailed description will now follow. Figure 6 The components of the computing device 600 shown.
[0087] Communication interface 602 can be configured to communicate with one or more computing devices. Examples of communication interface 602 include, but are not limited to, wired network interfaces (such as network interface cards), wireless network interfaces (such as wireless network interface cards), modems, audio / video connections, and any other suitable interfaces.
[0088] Processor 604 generally refers to any type or form of processing unit capable of processing data and / or interpreting, executing, and / or directing one or more of the instructions, procedures, and / or operations described herein. Processor 604 can perform operations by executing computer-executable instructions 612 (e.g., applications, software, code, and / or other executable data instances) stored in storage device 606.
[0089] Storage device 606 may include one or more data storage media, devices, or configurations, and may take the form of any type, form, and combination of data storage media and / or devices. For example, storage device 606 may include, but is not limited to, any combination of non-volatile media and / or volatile media described herein. Electronic data (including the data described herein) may be stored temporarily and / or permanently in storage device 606. For example, data representing computer-executable instructions 612 configured to boot processor 604 to perform any of the operations described herein may be stored within storage device 606. In some examples, data may be arranged in one or more databases residing within storage device 606.
[0090] I / O module 608 may include one or more I / O modules configured to receive user input and provide user output. One or more I / O modules may be used to receive input for a single virtual experience. I / O module 608 may include any hardware, firmware, software, or combinations thereof that support input and output capabilities. For example, I / O module 608 may include hardware and / or software for capturing user input, including but not limited to a keyboard or keypad, a touchscreen component (e.g., a touchscreen display), a receiver (e.g., an RF or infrared receiver), a motion sensor, and / or one or more input buttons.
[0091] I / O module 608 may include one or more devices for presenting output to a user, including but not limited to a graphics engine, a display (e.g., a screen), one or more output drivers (e.g., display drivers), one or more audio speakers, and one or more audio drivers. In some embodiments, I / O module 608 is configured to provide graphical data to a display for presentation to a user. The graphical data may represent one or more graphical user interfaces and / or any other graphical content that may be available for a particular implementation.
[0092] In some examples, any of the systems, computing devices, and / or other components described herein may be implemented by computing device 600. For example, memory 502 may be implemented by storage device 606, and processor 504 may be implemented by processor 604.
[0093] Figure 7 A flowchart 700 illustrates an example method for controlling a dual-frequency power supply system according to some embodiments of the present disclosure. While the flowchart depicts exemplary operations according to some embodiments, other embodiments may omit, add, reorder, and / or modify any operations shown in the flowchart. In some specific embodiments, one or more operations shown in the flowchart may be performed by a controller such as controller 112, computing device 206, etc.
[0094] This example method includes, at operation 702, detecting conditions for switching the operating mode of the dual-frequency power supply system from a first operating mode to a second operating mode. Operation 702 can be performed in any of the ways described herein.
[0095] The example method includes, at operation 704, switching the dual-frequency power system from operation in a first mode to operation in a second mode based on the detection of the condition. Operation 704 can be performed in any of the ways described herein. For example, operation 704 may include: disconnecting the signal generator (e.g., an RF generator) of the dual-frequency power system from a first transformer circuit configured to resonate at a first frequency and supply a first transformed voltage to an output coupled to a multipole electrode based on a signal voltage; setting the signal generator of the dual-frequency power system to switch from outputting a signal voltage at the first frequency to outputting a signal voltage at the second frequency; and connecting the signal generator of the dual-frequency system to a second transformer circuit configured to resonate at a second frequency and supply a second transformed voltage to an output coupled to a multipole electrode based on a signal voltage.
[0096] Those skilled in the art will recognize that, although various exemplary embodiments have been described with reference to the accompanying drawings in the foregoing description, it will be apparent that various modifications and alterations can be made thereto, and additional embodiments can be implemented, without departing from the scope of the invention as set forth in the appended claims. For example, certain features of one embodiment described herein may be combined with or substituted for features of another embodiment described herein. Therefore, the description and drawings should be considered illustrative rather than restrictive.
[0097] For example, while the described embodiments include an x-bar DC source 310 and a y-bar DC source 312 configured to provide differential DC voltages to a set of electrodes 302, the methods and systems described herein are applicable to any other suitable circuit topology. For instance, a multi-line topology configured to provide AC voltages in addition to the RF drive voltage (e.g., for an ion trap or any other suitable multipole structure) can be combined with features of the systems described herein, such as a switching circuit 316 (including any suitable modifications) configured to connect a power supply to one of two transformer assemblies to provide a dual-frequency RF generation system. Example multi-line topologies that can be appropriately modified to use the power supply systems taught herein can be found in U.S. Patent 6,844,547, the entire contents of which are incorporated herein by reference.
[0098] The advantages and features of this disclosure are further described in the following statements: 1. An apparatus for performing mass spectrometry analysis, the apparatus comprising: a set of multipole electrodes; an RF generator configured to selectively output an RF voltage at a first resonant frequency or a second resonant frequency to drive the set of multipole electrodes; a low-frequency transformer assembly; a high-frequency transformer assembly; and a switching circuit configured to: connect the RF generator to the low-frequency transformer assembly when the RF generator outputs the RF voltage at the first resonant frequency, the low-frequency transformer assembly being configured to supply a first voltage to an output coupled to the set of multipole electrodes based on the RF voltage; or connect the RF generator to the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly being configured to supply a second voltage to the output coupled to the set of multipole electrodes based on the RF voltage.
[0099] 2. The apparatus according to any one of the foregoing statements, wherein the switching circuit includes a first low-pass network for filtering the power of harmonics at the first resonant frequency and a second low-pass network for filtering the power of harmonics at the second resonant frequency.
[0100] 3. The apparatus according to any one of the foregoing statements, wherein the first low-pass network and the second low-pass network provide impedance transformation between the RF generator and the output.
[0101] 4. The apparatus according to any one of the foregoing statements, further comprising a controller connected to the RF generator and the switching circuit, and configured to selectively operate in a first mode or a second mode, wherein: in the first mode, the controller configures the RF generator to output the RF voltage at the first resonant frequency, configures the switching circuit to connect the RF generator and the low-frequency transformer assembly, and configures the switching circuit to disconnect the RF generator from the high-frequency transformer assembly; and in the second mode, the controller configures the RF generator to output the RF voltage at the second resonant frequency, configures the switching circuit to connect the RF generator and the high-frequency transformer assembly, and configures the switching circuit to disconnect the RF generator from the low-frequency transformer assembly.
[0102] 5. The apparatus according to any one of the preceding statements, further comprising a quadrupole mass filter including the set of multipole electrodes, wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions in a first mass-to-charge ratio (m / z) range, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions in a second m / z range below the first m / z range.
[0103] 6. The apparatus according to any one of the foregoing statements, further comprising a quadrupole mass filter including the set of multipole electrodes, wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions exceeding a threshold m / z value, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions exceeding a threshold m / z resolution.
[0104] 7. The apparatus according to any one of the foregoing statements, wherein the first resonant frequency is less than half of the second resonant frequency.
[0105] 8. The apparatus according to any one of the foregoing statements, wherein the switching circuit is configured to switch the connection between the high-frequency transformer assembly and the low-frequency transformer assembly in less than 10 milliseconds.
[0106] 9. The apparatus according to any one of the foregoing statements, wherein both the low-frequency transformer assembly and the high-frequency transformer assembly comprise an air-core transformer.
[0107] 10. The apparatus according to any one of the foregoing statements, wherein the low-frequency transformer assembly comprises a split transformer having two halves, and the apparatus further comprises a capacitor connected across the two halves of the low-frequency transformer assembly.
[0108] 11. A dual-frequency power supply system for driving multipole electrodes, the dual-frequency power supply system comprising: an RF generator configured to selectively output an RF voltage at a first resonant frequency or a second resonant frequency for driving the multipole electrodes; a low-frequency transformer assembly; a high-frequency transformer assembly; and a switching circuit configured to: connect the RF generator to the low-frequency transformer assembly when the RF generator outputs the RF voltage at the first resonant frequency, the low-frequency transformer assembly being configured to supply a first voltage to an output coupled to the set of multipole electrodes based on the RF voltage; or connect the RF generator to the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly being configured to supply a second voltage to an output coupled to the set of multipole electrodes based on the RF voltage.
[0109] 12. The system according to any one of the foregoing statements, wherein the switching circuit includes a first low-pass network for filtering the power of harmonics at the first resonant frequency and a second low-pass network for filtering the power of harmonics at the second resonant frequency.
[0110] 13. The system according to any one of the foregoing statements, wherein the first low-pass network and the second low-pass network provide impedance transformation between the RF generator and the output.
[0111] 14. The system according to any one of the foregoing statements, further comprising a controller connected to the RF generator and the switching circuit, and configured to selectively operate in a first mode or a second mode, wherein: in the first mode, the controller configures the RF generator to output the RF voltage at the first resonant frequency, configures the switching circuit to connect the RF generator and the low-frequency transformer assembly, and configures the switching circuit to disconnect the RF generator from the high-frequency transformer assembly; and in the second mode, the controller configures the RF generator to output the RF voltage at the second resonant frequency, configures the switching circuit to connect the RF generator and the high-frequency transformer assembly, and configures the switching circuit to disconnect the RF generator from the low-frequency transformer assembly.
[0112] 15. The system according to any one of the foregoing statements, further comprising a quadrupole mass filter including the multipole electrode, wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions in a first mass-to-charge ratio (m / z) range, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions in a second m / z range below the first m / z range.
[0113] 16. The system according to any one of the foregoing statements, further comprising a quadrupole mass filter including the multipole electrode, wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions exceeding a threshold m / z value, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions exceeding a threshold m / z resolution.
[0114] 17. The system according to any one of the foregoing statements, wherein the first resonant frequency is less than half of the second resonant frequency.
[0115] 18. The system according to any one of the foregoing statements, wherein the switching circuit is configured to switch the connection between the high-frequency transformer assembly and the low-frequency transformer assembly in less than 10 milliseconds.
[0116] 19. The system according to any one of the foregoing statements, wherein both the low-frequency transformer assembly and the high-frequency transformer assembly comprise an air-core transformer.
[0117] 20. The system according to any one of the foregoing statements, wherein the low-frequency transformer assembly includes a split transformer having two halves, and the system further includes a capacitor connected across the two halves of the low-frequency transformer assembly.
[0118] 21. A method for controlling a dual-frequency power supply system to drive a multipole electrode, the method comprising: detecting a condition when the dual-frequency power supply system is operating in the first mode; and, based on detecting the condition, switching the dual-frequency power supply system from operating in the first mode to operating in the second mode, the "switching" operation comprising: disconnecting an RF generator of the dual-frequency power supply system from a first transformer assembly configured to supply a first voltage to an output coupled to the multipole electrode based on the RF voltage when the RF generator outputs an RF voltage at a first resonant frequency; configuring the RF generator of the dual-frequency power supply system to switch from outputting the RF voltage at the first resonant frequency to outputting the RF voltage at a second resonant frequency; and connecting the RF generator of the dual-frequency power supply system to a second transformer assembly configured to supply a second voltage to the output coupled to the multipole electrode based on the RF voltage.
Claims
1. An apparatus for performing mass spectrometry analysis, the apparatus comprising: A set of multipole electrodes; An RF generator configured to selectively output an RF voltage at a first resonant frequency or a second resonant frequency for driving the set of multipole electrodes; Low-frequency transformer components; High-frequency transformer components; and The switching circuit is configured to: When the RF generator outputs the RF voltage at the first resonant frequency, the RF generator is connected to the low-frequency transformer assembly, which is configured to supply a first voltage to the output of the set of multipole electrodes based on the RF voltage. Alternatively, the RF generator can be connected to the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency. The high-frequency transformer assembly is configured to supply a second voltage to the output terminal coupled to the set of multipole electrodes based on the RF voltage.
2. The apparatus of claim 1, wherein the switching circuit includes a first low-pass network for filtering the power of harmonics at the first resonant frequency and a second low-pass network for filtering the power of harmonics at the second resonant frequency.
3. The apparatus of claim 2, wherein the first low-pass network and the second low-pass network provide impedance transformation between the RF generator and the output.
4. The apparatus of claim 1, further comprising a controller connected to the RF generator and the switching circuit, and configured to selectively operate in a first mode or a second mode, wherein: In the first mode, the controller configures the RF generator to output the RF voltage at the first resonant frequency, configures the switching circuit to connect the RF generator and the low-frequency transformer assembly, and configures the switching circuit to disconnect the RF generator from the high-frequency transformer assembly; and In the second mode, the controller sets the RF generator to output the RF voltage at the second resonant frequency, sets the switching circuit to connect the RF generator and the high-frequency transformer assembly, and sets the switching circuit to disconnect the RF generator from the low-frequency transformer assembly.
5. The apparatus of claim 1, further comprising a quadrupole mass filter, the quadrupole mass filter including the set of multipole electrodes, and The first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions in a first mass-to-charge ratio (m / z) range, and the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions in a second m / z range lower than the first m / z range.
6. The apparatus of claim 1, further comprising a quadrupole mass filter, the quadrupole mass filter including the set of multipole electrodes, and The first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions exceeding the threshold m / z value, and the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions exceeding the threshold m / z resolution.
7. The apparatus according to claim 1, wherein the first resonant frequency is less than half of the second resonant frequency.
8. The apparatus of claim 1, wherein the switching circuit is configured to switch the connection between the high-frequency transformer assembly and the low-frequency transformer assembly in less than 10 milliseconds.
9. The apparatus of claim 1, wherein both the low-frequency transformer assembly and the high-frequency transformer assembly comprise an air-core transformer.
10. The apparatus of claim 1, wherein the low-frequency transformer assembly comprises a split transformer having two halves, and the apparatus further comprises a capacitor connected across the two halves of the low-frequency transformer assembly.
11. A dual-frequency power supply system for driving multipole electrodes, the dual-frequency power supply system comprising: An RF generator configured to selectively output an RF voltage at a first resonant frequency or a second resonant frequency for driving the multipole electrodes; Low-frequency transformer components; High-frequency transformer components; and The switching circuit is configured to: When the RF generator outputs the RF voltage at the first resonant frequency, the RF generator is connected to the low-frequency transformer assembly, which is configured to supply a first voltage to the output terminal coupled to the multipole electrode based on the RF voltage. Alternatively, the RF generator can be connected to the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency. The high-frequency transformer assembly is configured to supply a second voltage to the output of the multipole electrode based on the RF voltage.
12. The system of claim 11, wherein the switching circuit includes a first low-pass network for filtering the power of harmonics at the first resonant frequency and a second low-pass network for filtering the power of harmonics at the second resonant frequency.
13. The system of claim 12, wherein the first low-pass network and the second low-pass network provide impedance transformation between the RF generator and the output.
14. The system of claim 11, further comprising a controller connected to the RF generator and the switching circuit, and configured to selectively operate in a first mode or a second mode, wherein: In the first mode, the controller configures the RF generator to output the RF voltage at the first resonant frequency, configures the switching circuit to connect the RF generator and the low-frequency transformer assembly, and configures the switching circuit to disconnect the RF generator from the high-frequency transformer assembly; and In the second mode, the controller sets the RF generator to output the RF voltage at the second resonant frequency, sets the switching circuit to connect the RF generator and the high-frequency transformer assembly, and sets the switching circuit to disconnect the RF generator from the low-frequency transformer assembly.
15. The system of claim 11, further comprising a quadrupole mass filter including the multipole electrode, and The first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions in a first mass-to-charge ratio (m / z) range, and the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions in a second m / z range lower than the first m / z range.
16. The system of claim 11, further comprising a quadrupole mass filter including the multipole electrode, and The first voltage at the first resonant frequency enables the quadrupole mass filter to filter out ions exceeding the threshold m / z value, and the second voltage at the second resonant frequency enables the quadrupole mass filter to filter out ions exceeding the threshold m / z resolution.
17. The system of claim 11, wherein the first resonant frequency is less than half of the second resonant frequency.
18. The system of claim 11, wherein the switching circuit is configured to switch the connection between the high-frequency transformer assembly and the low-frequency transformer assembly in less than 10 milliseconds.
19. The system of claim 11, wherein both the low-frequency transformer assembly and the high-frequency transformer assembly comprise an air-core transformer.
20. The system of claim 11, wherein the low-frequency transformer assembly comprises a split transformer having two halves, and the system further comprises a capacitor connected across the two halves of the low-frequency transformer assembly.
21. A method for controlling a dual-frequency power supply system to drive a multipole electrode, the method comprising: When the dual-frequency power supply system operates in the first mode, the detection conditions are as follows: as well as Based on the detected condition, the dual-frequency power system is switched from operating in the first mode to operating in the second mode, the "switching" operation including: The RF generator of the dual-frequency power supply system is disconnected from the first transformer assembly, which is configured to supply a first voltage to the output terminal coupled to the multipole electrode based on the RF voltage when the RF generator outputs an RF voltage at a first resonant frequency. The RF generator of the dual-frequency power supply system is configured to switch from outputting an RF voltage at the first resonant frequency to outputting an RF voltage at the second resonant frequency; and The RF generator of the dual-frequency power supply system is connected to a second transformer assembly, which is configured to supply a second voltage to the output terminal coupled to the multipole electrode based on the RF voltage.