Dual-frequency power system for mass spectrometry

Abstract

An example system includes a set of multipole electrodes and an RF generator configured to selectively output a signal voltage at a first frequency or at a second frequency for driving the set of multipole electrodes. The system further includes a low-frequency transformer assembly and a high-frequency transformer assembly. The system further includes 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 configured to supply a first voltage based on the RF voltage to an output coupled to the set of multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the set of multipole electrodes.

Description

DUAL-FREQUENCY POWER SYSTEM FOR MASS SPECTROMETRYRELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 589,568, filed October 11 , 2023, the contents of which is hereby incorporated by reference in its entirety.BACKGROUND INFORMATION

[0002] A mass spectrometer may be used to detect, identify, and / or quantify molecules based on the mass-to-charge ratio (m / z) of ions produced from the molecules. A mass spectrometer generally includes an ion source for producing ions from molecules included in a sample, a mass analyzer for separating the ions based on their m / z, and an ion detector for detecting the separated ions. The 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 that shows a relative abundance of each of the detected ions as a function of m / z. The mass spectrum may be used to detect and quantify molecules in simple and complex mixtures. In some configurations, a separation system, such as a liquid chromatograph (LC), gas chromatograph (GC), or capillary electrophoresis (CE) system, is coupled to the mass spectrometer in a combined system (e.g., LC-MS, GC-MS, or CE-MS system) to separate analytes in the sample before the analytes are introduced to the mass spectrometer.

[0003] One application of mass spectrometry is the identification, quantification, and structural elucidation of peptides, proteins, and related molecules in complex biological samples. In some such experiments, often referred to as multi-stage mass spectrometry (MSn where n is 2 or more) or tandem mass spectrometry (MS / MS or MS2 (n=2)), certain ions (referred to as precursor ions) are isolated and fragmented in a controlled manner to yield product ions. A mass analysis is then performed on the product ions to generate mass spectra of the product ions. The mass spectra of the product ions provide information that may be used to confirm identification, determine quantity, and / or derive structural details regarding analytes of interest.

[0004] Based on the different sizes of such molecules, the mass spectrometer may filter for a particular m / z range. However, due to the precision and magnitude ofinput power characteristics utilized by high-performance components of the mass spectrometer, configuring the mass spectrometer to be able to filter for all practical m / z ranges may be difficult.SUMMARY

[0005] The following description presents a simplified summary of one or more aspects of the methods and systems described herein to provide a basic understanding of such aspects. This summary is not an extensive overview of all contemplated aspects and is intended to neither identify key or critical elements of all aspects nor delineate the scope of any or all aspects. Its sole purpose is to present some concepts of one or more aspects of the methods and systems described herein in a simplified form as a prelude to the more detailed description that is presented below.

[0006] In some illustrative examples, an apparatus for performing mass spectrometry includes: a set of multipole electrodes; an RF generator configured to selectively output an RF voltage at a first resonant frequency or at a second resonant frequency for driving 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 configured to supply a first voltage based on the RF voltage to an output coupled to the set of multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the set of multipole electrodes.

[0007] In some illustrative examples, a dual-frequency power system to drive multipole electrodes includes: an RF generator configured to selectively output an RF voltage at a first resonant frequency or at 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 transformerassembly configured to supply a first voltage based on the RF voltage to an output coupled to the set of multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly configured to supply a second voltage based on the RF voltage to an output coupled to the set of multipole electrodes.

[0008] In some illustrative examples, a method for controlling a dual-frequency power system to drive multipole electrodes includes: detecting, while the dualfrequency power system is operating in a first mode, a condition; and causing, based on the detecting the condition, the dual-frequency power system to switch from operating in the first mode to operating in a second mode, the causing comprising: causing an RF generator of the dual-frequency power system to disconnect from a first transformer assembly configured to supply a first voltage based on an RF voltage to an output coupled to the multipole electrodes when the RF generator outputs the RF voltage at a first resonant frequency; setting the RF generator of the dual-frequency power system to switch from outputting the RF voltage at the first resonant frequency to outputting the RF voltage at a second resonant frequency; and causing the RF generator of the dual-frequency power system to connect to a second transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the multipole electrodes.BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The accompanying drawings illustrate various embodiments and are a part of the specification. The illustrated embodiments are merely examples and do not limit the scope of the disclosure. Throughout the drawings, identical or similar reference numbers designate identical or similar elements.

[0010] FIG. 1 A shows an illustrative implementation of a mass spectrometer including an ion accumulator.

[0011] FIG. 1 B shows another illustrative implementation of a mass spectrometer including a trapping-type mass analyzer.

[0012] FIG. 2 shows a functional diagram of an illustrative mass spectrometry system.

[0013] FIG. 3 shows an illustrative implementation of a mass analyzer.

[0014] FIG. 4 shows an illustrative implementation of a portion of a power system for a mass analyzer.

[0015] FIG. 5 shows a functional diagram of an illustrative control system.

[0016] FIG. 6 shows an illustrative computing device.

[0017] FIG. 7 shows an illustrative method for controlling a power system for a mass analyzer.DETAILED DESCRIPTION

[0018] A dual-frequency power system for mass spectrometry is described herein. The dual-frequency power system may enable the mass spectrometer to operate in two different modes that filter ions in different m / z ranges. The different m / z ranges may include not only a higher m / z range and a lower m / z range, but also m / z ranges of different widths, which may allow the mass spectrometer to filter at different m / z resolutions.

[0019] To enable this feature, the dual-frequency power system may include a topology configured to switch a signal generator to drive one of two transformer circuits, depending on the frequency of the output signal being generated by the signal generator. By connecting the signal generator to one of the transformers while disconnecting the signal generator from the other, the dual-frequency power system may be able to output power at two different frequencies with optimal power transfer to components of the mass spectrometer (e.g., a mass analyzer, a multipole system, a quadrupole filter, etc.). Moreover, the dual-frequency power system can enable a single system to detect ions across a broader combined range of mass-to-charge ratios while still maintaining high sensitivity and selectivity (i.e. , isolation widths), particularly for ions with low mass-to-charge ratio.

[0020] As used herein, “Th” or “Thomson” is a unit of mass-to-charge ratio equivalent to 1 Dalton (or atomic mass unit) per elementary electric charge.

[0021] Various examples will now be described in more detail with reference to the figures. The systems and methods described herein may provide one or more of the benefits mentioned above and / or various additional and / or alternative benefits that will be made apparent herein.

[0022] The dual-frequency power system described may be utilized by any suitable mass spectrometer. Various implementations of mass spectrometers will now be described. These implementations are illustrative only, and otherimplementations of mass spectrometers may be used in connection with the embodiments described here, such as a liquid chromatography-mass spectrometry (LC-MS) system, a high-performance liquid chromatography-mass spectrometry (HPLC-MS) system, a gas chromatography-mass spectrometry (GC-MS) system, or a capillary electrophoresis-mass spectrometry (CE-MS) system. The methods and systems described herein may also operate in conjunction with any other continuous flow sample source, such as a flow-injection mass spectrometry system (FI-MS) in which analytes are injected into a mobile phase (without separation in a column) and enter the mass spectrometer with time-dependent variations in intensity (e.g., Gaussian-like peaks).

[0023] FIG. 1 A shows a functional diagram of a first illustrative implementation 100A of a mass spectrometer 102. As shown, mass spectrometer 102 includes an ion source 104, an ion accumulator 106, an m / z analyzer 108 (which analyzes ions based upon their mass-to-charge, or m / z, ratio but is frequently referred to colloquially as a mass analyzer 108), a detector 110, and a controller 112. Mass spectrometer 102 may further include any additional or alternative components not shown as may suit a particular implementation (e.g., ion optics, filters, ion storage devices, ion mobility analyzers, etc.).

[0024] Ion source 104 is configured to produce a stream of ions 114 from the components eluting from, for example, a liquid chromatograph and deliver ion stream 114 to ion accumulator 106. Ion source 104 may use any suitable ionization technique, including without limitation electron ionization, chemical ionization, matrix assisted laser desorption / ionization, electrospray ionization, atmospheric pressure chemical ionization, atmospheric pressure photoionization, inductively coupled plasma, and the like. Ion source 104 may include various components for producing ions from components included in a sample and delivering the ions to ion accumulator 106.

[0025] Ion accumulator 106 is a device configured to accumulate, over an accumulation time, ions included in ion stream 114. In some examples, ion accumulator 106 is an ion storage device configured to buffer down-stream processes, such as mass analysis, thereby increasing scan speed and instrument sensitivity. In some examples, ion accumulator 106 is a beam-type device or a trapping device, such as a multipole ion guide (e.g., a quadrupole ion guide, a hexapole ion guide, an octapole ion guide, etc.), a linear quadrupole ion trap, athree-dimensional quadrupole ion trap, a cylindrical ion trap, a toroidal ion trap, an orbital electrostatic trap, a Kingdon trap, and the like. The accumulation of ions in ion accumulator 106 may be regulated with the aim to achieve a target number of ions in ion accumulator 106. Regulation of the accumulation of ions in ion accumulator 106 may, in some examples, be performed by a gate apparatus (not shown) that either transmits or blocks ion stream 114. The accumulated ions may then be transferred as ion stream 116 from ion accumulator 106 to mass analyzer 108.

[0026] Mass analyzer 108 is configured to isolate or separate ions in ion stream 116 according to m / z of each of the ions to filter and / or perform a mass analysis of the ions and frequently provide an ion stream 118 to detector 110. Mass analyzer 108 may be implemented by any suitable mass analyzer including a multipole structure, such as a quadrupole mass filter, an ion trap (e.g., a linear quadrupole ion trap, a three-dimensional quadrupole ion trap, a cylindrical ion trap, a toroidal ion trap, etc.), a time-of-flight (TOF) mass analyzer, an electrostatic trap mass analyzer (e.g. an orbital electrostatic trap such as an Orbitrap mass analyzer, a Kingdon trap, etc.), a Fourier transform ion cyclotron resonance (FT-ICR) mass analyzer, a sector mass analyzer, and the like. While the term “quadrupole” is used occasionally herein as a descriptor for a mass analyzer structure, it will be understood by one of ordinary skill in the art that the techniques, systems, and methods taught herein are not limited to structural implementations with four rods and that other multipole structures (i.e., hexapoles, octupoles) can be used in conjunction with the taught techniques, systems, and methods.

[0027] In some examples, mass spectrometer 102 is a tandem mass spectrometer (tandem-in-time or tandem-in-space) configured to perform tandem mass spectrometry (e.g., MS / MS), a multi-stage mass spectrometer configured to perform multi-stage mass spectrometry (also denoted MSn), or a hybrid mass spectrometer. For example, mass analyzer 108 may include multiple mass analyzers (e.g., m / z analyzers), mass filters (e.g., m / z filters), and / or collision cells. The term “collision cell,” as used herein, may include any structure or device configured to produce product ions via controlled dissociation processes, ion-neutral or ion-ion reaction processes and is not limited to devices employed for collisionally-activated dissociation. For example, a collision cell may be configured to fragment the ions using collision induced dissociation (CID), electron transfer dissociation (ETD), electron capture dissociation (ECD), photo induced dissociation (PID), surfaceinduced dissociation (SID), and the like. A collision cell may be positioned upstream from a mass filter, which separates the fragmented ions based on the ratio of mass to charge of the ions. 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, where a collision cell is interposed in the ion path between independently operable mass filters.

[0028] While FIG. 1A shows that ion accumulator 106 is positioned upstream from mass analyzer 108, ion accumulator 106 may be positioned at any other location along an ion path from ion source 104 to detector 110 within a tandem mass spectrometer or multi-stage mass spectrometer (e.g., between a first mass filter (Q1 ) and a collision cell (Q2) and / or between a collision cell (Q2) and a 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 multi-stage mass spectrometer.

[0029] Ion detector 110 is configured to detect ions either within the mass analyzer 108 or in ion stream 118 from the mass analyzer 108 at each of a variety of different m / z and responsively generate an electrical signal representative of ion intensity. The electrical signal is transmitted to controller 112 for processing, such as to construct 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 the 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 may be implemented by any suitable detection device, including without limitation an electron multiplier, a Faraday cup, and the like.

[0030] Controller 112 may be communicatively coupled with, and configured to control various operations of, mass spectrometer 102. For example, controller 112 may be configured to control operation of various hardware components included in ion source 104, ion accumulator 106, mass analyzer 108, and / or detector 110. To illustrate, controller 112 may be configured to control an accumulation time of ion accumulator 106 and / or mass analyzer 108, control an oscillatory voltage power supply and / or a DC power supply to supply an RF voltage and / or a DC voltage to mass analyzer 108, adjust values of the RF voltage and DC voltage to select an effective m / z (including a mass tolerance window) for analysis, and adjust the sensitivity of ion detector 110 (e.g., by adjusting the detector gain).

[0031] Controller 112 may include any suitable hardware (e.g., a processor, circuitry, etc.) and / or software as may serve a particular implementation. While FIG. 1A shows that controller 112 is included in mass spectrometer 102, controller 112 may alternatively be implemented in whole or in part separately from mass spectrometer 102, such as by a computing device communicatively coupled to mass spectrometer 102 by way of a wired connection (e.g., a cable) and / or a network (e.g., a local area network, a wireless network (e.g., Wi-Fi), a wide area network, the Internet, a cellular data network, etc.). In some examples, controller 112 may be implemented in whole or in part by Control module 256 (and vice versa).

[0032] FIG. 1 B shows a functional diagram of another illustrative implementation 100B of mass spectrometer 102. Implementation 100B is similar to implementation 100A except that, in implementation 100B, mass analyzer 108 is a trapping-type mass analyzer and ion accumulator 106 and ion stream 116 from ion accumulator 106 are omitted. Ions are accumulated in mass analyzer 108 over an accumulation time to achieve a target number of ions in mass analyzer 108. In some embodiments, the mass spectrometer 102 can include an electrostatic trap mass analyzer / detector such as an Orbitrap™ analyzer that can combine features of the mass analyzer 108 and the detector 110 into a single component or device.

[0033] FIG. 2 illustrates example environment 200 within which the dualfrequency power systems described herein may operate. Specifically, environment 200 includes an example mass spectrometer system 204 for complex mass spectrometry experiments, and computing devices 206 configured to control the operation of mass spectrometer system 204 and / or perform post processing on detector data generated therefrom. While the present disclosure describes environments that include mass spectrometers, in some embodiments environment 200 may include a different type of system that is configured to manipulate and / or otherwise examine ions within an ion trap.

[0034] FIG. 2 shows mass spectrometer system 204 as being a hybrid mass spectrometer 210 including more than one type of mass analyzer. Specifically, mass spectrometer 210 includes an ion trap mass analyzer 208 as well as an optional electrostatic trap mass analyzer 212 (e.g., ORBITRAP™ analyzer). However, it is understood that different combinations of mass analyzers may be used for different applications, and thus mass spectrometer system 204 may include a fewer orgreater number of mass analyzers and / or comprise different combinations of mass analyzers.

[0035] In operation of mass spectrometer 210, an electrospray ion source 214 provides ions of a sample to be analyzed to an aperture of a heated ion transfer tube 216, at which point the ions enter into a first vacuum chamber 218. After entry, the ions are captured and focused into a tight beam by an ion collimating device 220 (e.g., a stacked-ring ion guide, an ion lens, an ion funnel, etc.). Mass spectrometer 210 is further shown as including a plurality of ion optical transfer components 222 (e.g., optical transfer components 222-1 through 222-4) that are configured to allow ions to pass between intermediate-vacuum regions of the mass spectrometer during travel. Mass spectrometer 210 is illustrated as including a curved beam guide 224 that separates most remaining neutral molecules and undesirable ion clusters (e.g., solvated ions, environmental contaminants, etc.) from the ion beam. For example, neutral molecules and ion clusters may follow a straight-line path whereas the paths of ions of interest may be bent around a ninety-degree turn of curved beam guide 224, thereby producing the separation.

[0036] An RF (Radio Frequency) quadrupole mass filter 226 of mass spectrometer 210 may be used as a tunable mass filter to pass ions within a selected m / z range. Ion optical transfer component 222-2 delivers the m / z filtered (m / z selected) ions to a curved ion trap (“C-trap”) component 228. C-trap 228 may be able to transfer ions along a pathway between quadrupole mass filter 226 and RF (Radio Frequency) ion trap mass analyzer 208. C-trap 228 may further be configured to temporarily collect and store a population of ions. C-trap 228 may then deliver the ions, as a pulse or packet, into mass analyzer 212.

[0037] FIG. 2 further shows a multipole ion guide 230 and optical transfer component 222-3 as serving to guide ions between C-trap 228 and ion trap mass analyzer 208. Multipole ion guide 230 may provide temporary ion storage capability such that ions produced in a first processing step of an analysis method can be later retrieved for processing in a subsequent step. RF multipole ion guide 230 may also serve as a fragmentation cell and ion trap (i.e., an ion routing multipole). Various ion optics along the pathway between C-trap 228 and ion trap mass analyzer 208 may be controllable such that ions may be transferred in either direction, depending upon the sequence of ion processing steps required in a particular analysis method.

[0038] Ion trap mass analyzer 208 is illustrated in FIG. 2 as being a dual-pressure region RF quadrupole linear ion trap 232 (e.g., a two-dimensional trap mass analyzer) including a high-pressure linear trap cell 234 and a low-pressure linear trap cell 236, the two cells being positioned adjacent to one another and separated by a plate lens having a small aperture that permits ion transfer between the two cells and that also acts as a pumping restriction that allows different pressures to be maintained in the two traps.

[0039] The environment of high-pressure cell 234 favors ion trapping, ion cooling, ion fragmentation by either collision-induced dissociation or pulsed-q dissociation, ion / ion reactions by either electron transfer dissociation or proton-transfer reactions, and some types of photon activation, such as ultraviolet photo dissociation (UVPD). The environment of low-pressure cell 236 favors analytical scanning with high resolving power and mass accuracy. The ion trap mass analyzer 208 further is shown as including an ion detector 238 (e.g., a dual-dynode ion detector).

[0040] The use of either electron transfer dissociation or a proton transfer reaction, within a mass analysis method, utilizes a capability of performing controlled ion-ion reactions within a mass spectrometer. Ion-ion reactions, in turn, utilize capabilities of generating reagent ions, and of causing the reagent ions to mix with sample ions. Mass spectrometer 210 is depicted as including a reagent-ion source 240 disposed between the stacked-ring ion guide and the curved beam guide 224. However, one or more additional reagent-ion sources may be included in an example mass spectrometer system.

[0041] FIG. 2 further illustrates mass spectrometer 210 as including one or more additional components 242. Such additional components may include various combinations of one or more ion guides, ion traps, lenses, detectors, reagent ion sources, etc. Mass spectrometer 210 is merely an example configuration of a system capable of enabling / performing the system and methods for dual m / z range filtering disclosed herein.

[0042] The environment 200 is also shown as including one or more computing devices 206. Computing devices 206 depicted in FIG. 2 are merely illustrative and are not intended to limit the scope of the present disclosure. Computing devices 206 may include any combination of hardware or software that can perform the indicated functions, including computers, network devices, internet appliances, PDAs, wireless phones, controllers, oscilloscopes, amplifiers, etc. Computing devices 206 may alsobe connected to other devices that are not illustrated, or instead may operate as a stand-alone system.

[0043] Further, one or more of computing devices 206 may be a component of mass spectrometer system 204, may be a separate device from mass spectrometer system 204 and in communication with the mass spectrometer system 204 via a network communication interface, or a combination thereof. For example, mass spectrometer system 204 may include a first computing device of computing devices 206 that is a component portion of mass spectrometer system 204, and that acts as a controller that drives an operation of mass spectrometer system 204 (e.g., adjust the scanning location on the sample by operating the scan coils, control the dualfrequency power system, etc.). In such an embodiment, mass spectrometer system 204 may also include a second computing device of computing devices 206, such as a computer separate from mass spectrometer system 204, and that is executable to process detector data received from ion detector 238 to generate representations of the spectra based on the detector data (e.g., chromatograms, extracted ion current (EIC) profiles, etc.) and / or perform other types of analysis or post-processing of the detector data. Computing devices 206 may further be configured to receive user selections via a keyboard, mouse, touchpad, touchscreen, wireless devices, other user interface, etc.

[0044] Additionally, computing device(s) 206 may be configured to control mass spectrometer system 204 to allow for performing a mass spectrometry analysis on a sample. For example, one or more user selections, an automation program, or a combination thereof may allow computing devices 206 to cause mass spectrometer system 204 and / or components thereof to perform any of the methods described in the present disclosure, and using any of the parameters described herein. User selections, an automation program, or a combination thereof may then cause computing devices 206 to generate and / or analyze detector data from the mass spectrometer system 204 relating to a sample, and / or create one or more chromatograms associated with the performed mass spectroscopy analysis of the samples.

[0045] FIG. 2 further includes a schematic diagram illustrating an example computing architecture 250 of computing devices 206. Computing architecture 250 illustrates additional details of hardware and software components that may be used to implement one or more of the techniques described in the present disclosure.Computing architecture 250 may be implemented in a single computing device 206 or may be implemented across multiple computing devices 206. For example, individual modules and / or data constructs depicted in computing architecture 250 may be executed by and / or stored on different computing devices 206. In this way, different process steps of the methods disclosed herein may be executed and / or performed by separate computing devices 206 and in various orders within the scope of the present disclosure. In other words, the functionality provided by the illustrated components may in some implementations be combined in fewer components or distributed in additional components. Similarly, in some implementations, the functionality of some of the illustrated components may not be provided and / or other additional functionality may be available.

[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 the memory 254. As used herein, the term “module” is intended to represent example divisions of executable instructions for purposes of discussion and is not intended to represent any type of requirement or required method, manner, or organization. Accordingly, while various “modules” are described, their functionality and / or similar functionality could be arranged differently (e.g., combined into a fewer number of modules, broken into a larger number of modules, etc.). Further, while certain functions and modules are described herein as being implemented by software and / or firmware executable on a processor, in other instances, any or all of modules can be implemented in whole or in part by hardware (e.g., a specialized processing unit, etc.) to execute the described functions. As discussed above in various implementations, the modules described herein in association with computing architecture 250 can be executed across multiple computing devices 206.

[0047] Control module 256 may be executable by processors 252 to cause computing device 206 and / or mass spectrometer system 204 to take one or more actions and / or perform functions or maintenance of the systems. In some embodiments, control module 256 may cause mass spectrometer system 204 to perform a mass spectrometry analysis on a sample. More specifically, according to the present disclosure, control module 256 can be executable to cause mass spectrometer system 204 and / or components thereof to perform any of the methodsdescribed in the present disclosure, and using any of the parameters described herein.

[0048] As discussed above, computing devices 206 include one or more processors 252 configured to execute instructions, applications, or programs stored in a memory(s) 254 accessible to one or more processors 252. In some examples, one or more processors 252 may include hardware processors that include, without limitation, a hardware central processing unit (CPU), a graphics processing unit (GPU), and so on. While in many instances the techniques are described herein as being performed by one or more processors 252, in some instances the techniques may be implemented by one or more hardware logic components, such as a field programmable gate array (FPGA), a complex programmable logic device (CPLD), an application specific integrated circuit (ASIC), a system-on-chip (SoC), or a combination thereof.

[0049] Memories 254 accessible to one or more processors 252 are examples of computer-readable media. Computer-readable media may include two types of computer-readable media, namely computer storage media and communication media. Computer storage media may include volatile and non-volatile, removable, and non-removable media implemented in any method or technology for storage of 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 memory technology, compact disc read-only memory (CD-ROM), digital versatile disk (DVD), or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other non-transmission medium that may be used to store the desired information and which may be accessed by a computing device. In general, computer storage media may include computer executable instructions that, when executed by one or more processing units, cause various functions and / or operations described herein to be performed. In contrast, communication media embodies computer-readable instructions, data structures, program modules, or other data in a modulated data signal, such as a carrier wave, or other transmission mechanism. As defined herein, computer storage media does not include communication media. Those skilled in the art will also appreciate that items or portions thereof may be transferred between memory 254 and other storage devicesfor purposes of memory management and data integrity. Alternatively, in some implementations, some or all the software components may execute in memory on another device and communicate with computing devices 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 a portable article to be read by an appropriate drive, various examples of which are described above. In some implementations, instructions stored on a computer-accessible medium separate from computing devices 206 may be transmitted to computing devices 206 via transmission media or signals such as electrical, electromagnetic, or digital signals, conveyed via a communication medium such as a wireless link. Various implementations may further include receiving, sending, or storing instructions and / or data implemented in accordance with the foregoing description upon a computer-accessible medium.

[0050] Control module 256 and / or controller 112 may also include and / or provide a user interface configured to enable user interaction 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 by tactile, visual, auditory, and / or other sensory type communication. For example, the user interface may include a display device (e.g., liquid crystal display (LCD) display screen, a touch screen, etc.) for displaying information (e.g., mass spectra, notifications, etc.) to the user. The user interface may also include an input device (e.g., a keyboard, a mouse, a 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 separate from, but communicatively coupled to, control module 256 and / or controller 112. For instance, the display device and the input device may be included in a computer (e.g., a desktop computer, a laptop computer, etc.) communicatively connected to control module 256 and / or controller 112 by way of a wired connection (e.g., by one or more cables) and / or a wireless connection.

[0051] Control module 256 and / or controller 112 acquires data acquired over time by mass spectrometer system 204 and / or mass spectrometer 102. The data may include a series of mass spectra including intensity values of ions produced from the analytes of a sample as a function of m / z of the ions. The series of mass spectra may be represented in a three-dimensional map in which elution time (e.g., retention time) is plotted along an X-axis of the map, m / z is plotted along a Y-axis of the map,and intensity is plotted along a Z-axis of the map. Spectral features on the map (e.g., Z-axis peaks of intensity) represent detection by mass spectrometer system 204 and / or mass spectrometer 102 of ions produced from various analytes included in the sample. The X-axis and Z-axis of the map may be used to generate an elution profile (e.g., a mass chromatogram) that plots detected intensity as a function of time for a selected m / z.

[0052] In mass spectrometry, the m / z range for m / z selection of a RF quadrupole mass filter (which may implement a mass analyzer and / or other component within a mass spectrometer) depends on an operating frequency, f, a maximum magnitude of an RF voltage (2 b -peak, max ) that can be applied between x and y rod electrode pairs of the quadrupole mass filter, and a characteristic dimension, ro, of the quadrupole electrode assembly. For example, in some embodiments, where the RF voltage is varying sinusoidally, a maximum mass-to-charge ratio, (m / z)max, a quadrupole m / z filter may m / z select is determined approximately by the expression:where e = 1.902 x 10-19Coulombs / elementary charge, m = 1.66 x 10-27kilograms (kg) / Dalton (Da), (^ / z^max corresponds to an upper m / z (mass-to-number of elementary charge ratio) limit for m / z selection of the quadrupole mass filter, represents the quadrupole operating frequency in kilohertz (kHz), and r0describes a quadrupole characteristic dimension in millimeters (mm). In example embodiments, the ro of the quadrupole m / z filter electrode (hyperbolic profile ground on to round rod electrodes) assembly is in a range from 4 mm to 6 mm.

[0053] In conventional systems, the initial design of the instrument dictates values for ro (the dimensions of the assembly) and f that cannot easily be changed after production of the machine because of mechanical or electronic constraints as well as the design goal for the attainable m / z selection resolution and the efficiency of ion transmission through the device when operating at near the maximum attainable resolution and at the upper end of its m / z range. For a modern high performance mass spectrometer system like that depicted and described in relation to Fig. 2, the magnitude of 2Vo-peak, max is about 10,000 Volts at an operating frequency of about 1100 kHz. To make such large voltages without expending vast amounts of power, a tuned circuit voltage transformer network is used. These involve custom-built(typically air core) inductors capable of dissipating in excess of 100 Watts. The most widely used implementations conventionally involve using a large turned circuit transformer inductor assembly (e.g., the primary is a few turns and the secondary is many tens of turns) connected across the electrode pairs (capacitive load) of the m / z filter or quadrupole linear ion trap. When driven at the configuration’s resonant frequency, large voltages can be applied to the m / z analyzer’s electrodes. For example, the RF amplifier circuit and other electronics are selected and tuned to work optimally at the design frequency. If operated at a different frequency, resonant coupling will be reduced and unwanted Joule heating can arise. Thus, in operation, conventional systems can successfully manipulate ions within a pre-determined range of mass-to-charge ratios as determined by the above equation, and accessing a specific mass-to-charge ratio is a matter of adjusting the applied voltage, (2Vo-peak). In the case of the system being an m / z filter, a corresponding superposed similarly applied DC voltage may be adjusted to access the specific m / z ratio.

[0054] To access a higher value of (m / z)max, the maximum applied voltage may be increased. However, the maximum RF voltage magnitude may be limited by various factors, such as a voltage breakdown across insulators that separate the rod electrodes from each other and other conductive surfaces, or the wires delivering the voltage to or in the feed-throughs that deliver RF voltages into the vacuum chamber. The pressures a quadrupole m / z filter operates at may generally be too low to generate arcs, but breakdown across and sometimes through insulators may occur and result in permanent damage to the apparatus.

[0055] Additionally or alternatively, the maximum RF voltage may be limited by field emission induced by high electric fields resulting from the application of high RF voltage to the quadrupole m / z filter rod electrodes. The emission may come off of the rod electrodes or other counter electrodes in the vicinity. Generally field emission is not destructive, but it may cause interfering ion signal (noise) as well as other problems.

[0056] Additionally or alternatively, the maximum RF voltage may be limited by high voltage breakdown, arcing, or discharge in the tuned RF transformer circuitry (coils, capacitors, insulators etc.), electrical connections, or an atmospheric side of one or more vacuum feedthroughs that deliver the high voltage RF into the vacuum chamber where the quadrupole m / z filter electrode is located. Such breakdown may damage the apparatus. Very small amounts of discharge are generally sufficient tointerfere with regulation of the applied RF voltage magnitudes to the very high precision voltage utilized for proper operation of the RF quadrupole m / z analyzer.

[0057] Additionally or alternatively, depending on a size of the instrument and / or an instrument power budget, there may be practical constraints on the size and power output of the RF power amplifier driving the RF transformer. Because there may be rather extreme precision and drift requirements during regulation of a magnitude of the RF voltages applied to the rod electrodes, the RF amplifier driving the RF transformer may need relatively low distortion. For example, class AB type amplifiers that may be used may typically be 60% efficient (or lower) in converting input power supply power to output RF power. In one example, for a maximum selected m / z of 2,000 Th for the RF quadrupole m / z filter analyzer at a nominal operating frequency of 1 ,100 kHz, about 150 W of RF may be delivered to the primary of the transformer coil. Resistive losses in the transformer coil(s) represent a large fraction of consumption of this power. Resistive losses from eddy currents induced in a conductive aluminum box enclosing the RF transformer circuitry as well as RF absorption by various materials (e.g., glues, plastics, printed circuit board materials used for the coil form as well as connections etc.) for the overall assembly may cause additional losses. In some embodiments, a Litz wire may be used to reduce resistive losses in the transformer coils, and fan-driven forced convective cooling may be used to prevent overheating of the transformer coils and the entire assembly. The resistive losses may generally increase with frequency, so for a given electrode structure (fixed capacitance, fixed ro), to achieve a samen / z)m.ax, the RF power that may be required may increase with frequency, for instance, by something more than a f4relationship that may be expected from a quadratic relationship of voltage and power and the expression for (^ / z^max provided above.

[0058] Thus, for a number of reasons, it is often not practical to simply increase the maximum magnitude of applied RF voltage. As an alternative, one may consider reducing the frequency of operation to access a greater value form / z)max- Foragiven maximum amount of voltage that may be applied between the x- and y- rod electrode pairs, lowering the RF frequency may increase the upper limit for m / z selection as described in the above equation. However, reducing the operating frequency may reduce the efficiency of ion transmission through the device, and generally reduces the practical maximum resolving power of the device. For a m / z filter, reducing the operating frequency can increase a practical minimum m / ztransmission bandwidth (i.e. , isolation width) centered at a given m / z. For example, the isolation width for a multipole (e.g., an RF quadrupole m / z filter) may be as small as 0.4-1 Th when operated at high frequency but may be as large as 10-100 Th when operated at a sufficiently reduced frequency. As a result, the RF quadrupole m / z filter may generally exhibit lower ion transmission within the m / z transmission band (and thus lower instrument sensitivity), create a stronger dependence of ion transmission on kinetic energy, and introduce general irregularity in ion transmission within the m / z transmission band.

[0059] In practice, reductions in a quadrupole filter’s operating frequency may result in poorer m / z peak (line) shape and worse practical peak minimum widths, as well as degradation in m / z peak shape. Further, resolution of a distribution of ion (axial) velocities may be decreased (broadened minimum m / z transmission window width). Thus, a system designed to operate solely at low frequency to access a very high value of (m / z)max may have unacceptable resolution when isolating ions having low values of m / z (which have higher velocities for a given kinetic energy / charge). As described above, the alternative of simply utilizing a higher maximum RF voltage and higher power to extend the (^ / z^max may not generally be practical as the system may be designed to power and RF voltage limits and margins.

[0060] To address these problems, systems and methods described herein may include a multipole electrode structure (e.g., a quadrupole electric field imposing structure) and a dual-frequency power system (e.g., a dual-frequency RF generation system) that is configured to operate at two different frequencies and therefore have two different m / z ranges of operation. The dual-frequency RF generation system may include two transformer circuits (e.g., coil assemblies) and a switching circuit that is configured so that the system drives one of the two transformers while decoupling the other, depending on the frequency range of operation. Such a configuration may allow for rapid switching between filtering for two different m / z ranges with easier component design for an input impedance for optimal power transfer from an RF amplifier. The systems and methods taught herein enable the user to effectively m / z filter for ions having high values of m / z (e.g., in a range from 2000-8000 Th) while also retaining higher resolution when filtering ions having lower values of m / z (e.g., in a range from 50-2000) with the same m / z analyzer.

[0061] FIG. 3 shows an example configuration 300 of a multipole structure that may be a portion of a mass analyzer and an associated dual frequency powersystem 308. Specifically, configuration 300 shows a quadrupole electrode structure with a set of electrodes 302 including an x-rod electrode pair 304 (e.g., x-rod electrode 304-1 and 304-2) and a y-rod electrode pair 306 (e.g., y-rod electrode 306- 1 and 306-2) coupled to dual-frequency power system 308. Dual-frequency power system 308 may include an x-rod DC source 310 that is coupled to x-rod electrode pair 304 and drives x-rod electrode pair 304. Dual-frequency power system 308 may further include a y-rod DC source 312 that is coupled to y-rod electrode pair 306 and drives y-rod electrode pair 306. Dual-frequency power system 308 further includes an RF amplifier 314 configured to output a high-power RF voltage into a relatively low impedance load (for example 75 ohms) at a first frequency or at a second frequency, depending on an operating mode of the mass analyzer, that enables the mass analyzer to filter ions over a first m / z range or a second m / z range, respectively. RF amplifier 314 may output the signal voltage to a switching circuit 316.

[0062] Switching circuit 316 may be configured to connect RF amplifier 314 to one of two transformer assemblies in a single dual resonant frequency LC network to output a transformed high RF voltage within one of the two resonance frequency bands, depending on the operating mode. For instance, in a low-frequency operating mode, switching circuit 316 may connect RF amplifier 314 to a low-frequency transformer assembly 318 (which may include a primary winding 320, and a secondary winding 322 that can be implemented as a split winding including an x-rod secondary winding 322-1 and a y-rod secondary winding 322-2 as shown in FIG. 3) and disconnect RF amplifier 314 from a high-frequency transformer assembly 324 (which may include a primary winding 326, and a secondary winding 328 that can be implemented as a split winding including an x-rod secondary winding 328-1 and a y- rod secondary winding 328-2 as shown in FIG. 3). Conversely, in a high-frequency operating mode, switching circuit 316 may connect RF amplifier 314 to high- frequency transformer assembly 324 and disconnect RF amplifier 314 from low- frequency transformer assembly 318. In this manner, either low-frequency transformer assembly 318 or high-frequency transformer assembly 324 may be driven by RF amplifier 314 with a majority of the RF drive voltage to provide a low- frequency or high-frequency signal to the quadrupoles for either a high m / z filter range or a low m / z filter range, respectively.

[0063] For example, to operate the m / z analyzer with the higher or “extended” m / z range, RF amplifier 314 outputs an RF voltage at a frequency with the lower of the two resonant frequency bands of the transformer network. In some examples, the frequency of the low-frequency RF voltage can be in a range from 250-750 kHz or can be about 500 kHz. Switching circuit 316 connects RF amplifier 314 to primary winding 320 of low-frequency transformer assembly 318, while disconnecting RF amplifier 314 from primary winding 326 of high-frequency transformer assembly 324. As a result, low-frequency transformer assembly 318 and a low-frequency resonance capacitor 330 connected across both halves of secondary winding 322 act as the main resonant elements to supply the greater portion of the RF voltage step up to drive the quadrupole electrodes, with a lesser but not insignificant portion of the voltage step up from the inductance of the secondary winding 328 of high-frequency transformer assembly 324. Connecting the RF amplifier only with primary winding 320 of low-frequency transformer assembly 318 generally enables more straightforward design of primary winding 320 and primary winding 326 and impedance matching network circuitry within switching circuit 316. To obtain the maximum RF voltage magnitude across the x-rod and y-rod electrodes with the minimum power output that is within maximum power output available from RF amplifier 314, RF amplifier 314 drives amplifier output frequency to be very close to the lower resonant frequency of the voltage transformation network (at or very near resonance) that there may be proper impedance matching (and optionally, transformation) in the transmission of the RF power from the output of RF amplifier 314 and primary winding 320 of the transformer assembly. The network elements of the entire LC network, including the inductances of both secondary winding 322 of low frequency transformer assembly 318 and secondary winding 328 of high- frequency transformer assembly 324, low-frequency resonance capacitor 330, the capacitance of set of electrodes 302, any other capacitances across the x-rod electrodes 304 and y-rod electrodes 306 introduced by electrical feed-throughs, routing of the electrical connections etc., any other added capacitances, and the x- rod and y-rod electrode blocking capacitor 332, all combine to determine both the lower resonant frequency (center frequency of the narrow lower resonant frequency band) and the higher resonant frequency (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 transmission), RF amplifier 314 may output a high-frequency RF voltage (e.g., an RF voltage higher than a threshold frequency and / or lower than the low-frequency RF voltage). In some examples, the frequency of the high-frequency RF voltage can be in a range from 800 kHz to 1400 kHz or can be about 1100 kHz. Switching circuit 316 may connect RF amplifier 314 to primary winding 326 of high-frequency transformer assembly 324, while disconnecting RF amplifier 314 from primary winding 320 of low-frequency transformer assembly 318. As a result, high-frequency transformer assembly 324 and the quadrupole load (which may function as a capacitor in the circuit) may act as the main resonant circuit to supply a high-frequency transformed voltage to drive the quadrupoles with minimal influence from low-frequency transformer assembly 318, which, with low- frequency resonance capacitor 330 may operate somewhat like a short at the high- frequency RF voltage. Thus, again, this may allow for easier impedance matching to drive primary winding 326 of the high-frequency transformer assembly 324 at or near the transformer network’s high-frequency resonance.

[0065] The high m / z range and low m / z range may be any suitable m / z ranges, for example, based on the ion m / z filtering applications. Depending on the m / z ranges, suitable frequency ranges may be determined for the RF voltage, as well as other parameters of dual-frequency power system 308, such as the number of primary and secondary turns, secondary inductance, and / or other physical parameters of low-frequency transformer assembly 318 and high-frequency transformer assembly 324. For instance, the low m / z range (higher frequency operating mode) of the m / z filter may be approximately 50-2000 Th, which may be applicable for experiments involving small molecules and / or peptides. In some examples, the m / z selection width when the system is operated in the lower m / z range can be set in the range of 0.4 Th to 1 ,500 Th. The high m / z range (lower RF frequency) operating mode enables an extension of the m / z range for m / z selection from approximately 2000-8000 Th, which may be applicable for experiments involving proteins and / or protein complexes which ionize into that m / z range. In some examples, the m / z selection width when the system is operated in the extended m / z range mode (low RF frequency mode) can be chosen to be a value in the range of 5 Th to 3,000 Th. The low m / z range mode (higher frequency mode) generally allows for a higher resolution m / z selection (filtering) of ions, while the highm / z range allows for higher m / z magnitude. Thus, the high-frequency RF voltage may be a voltage that allows for any suitable m / z range that has a low-end limit (as one example, 50 Th) that is lower than the low-end limit (as one example, 2000 Th) of the m / z range enabled by the low-frequency RF voltage. Additionally or alternatively, the high-frequency RF voltage may be selected to allow for an m / z range that enables the mass analyzer to filter ions over a threshold m / z resolution level, while the low-frequency RF voltage may be selected to allow for an m / z range over a threshold m / z magnitude level. Advantages of the high frequency mode can include higher maximum resolution (i.e. , smallest accessible m / z peak widths are narrower than in other modes), higher ion transmission at a given resolution, and less sensitivity of m / z peak shape or resolution to ion velocity. Advantages of the low frequency mode can include greater values for maximum m / z for selection.

[0066] In some examples, the frequency of the low-frequency RF voltage may be set to be less than one-half the frequency of the high-frequency RF voltage. For instance, the frequency of the low-frequency RF voltage may be a predetermined amount (e.g., 40 kHz) less than one-half the frequency of the high-frequency RF voltage to avoid issues with harmonic components in the RF voltage.

[0067] Further, in some examples, dual-frequency power system 308 may include additional components and / or characteristics to eliminate harmonic signal components. For instance, low-frequency transformer assembly 318 and / or high- frequency transformer assembly 324 may be implemented by or include air-core transformers to reduce or eliminate generation of harmonic RF voltage components. Additionally, air-core transformers may reduce or minimize power losses that may occur due to non-linearities in magnetic properties of the core material.

[0068] Additionally or alternatively, dual-frequency power system 308 may further include additional filter components in or coupled to switching circuit 316. For example, FIG. 4 shows an example configuration 400 that shows components of switching circuit 316, with a few components of configuration 300 also shown for context. As in configuration 300, RF amplifier 314 is coupled to switching circuit 316, and switching circuit 316 may switch the coupling of RF amplifier 314 between primary winding 320 of low-frequency transformer assembly 318 and primary winding 326 of high-frequency transformer assembly 324. As shown, switching circuit 316 may include a pair of low-pass filters (e.g., low-pass filter 404 and low-pass filter 406). Low-pass filter 404 and low-pass filter 406 may be implemented in any suitable manner, such as passive low-pass dual pi network-type LC filters.

[0069] Switching circuit 316 may include two branches 402, branch 402-1 leading to low-frequency transformer assembly 318 and branch 402-2 leading to high- frequency transformer assembly 324. Each branch 402 may include two switching mechanisms with a low-pass filter in between. For example, branch 402-1 may include switches 408 (e.g., switch 408-1 and switch 408-2) coupled to low-pass filter 404. Similarly, branch 402-2 may include switches 410 (e.g., switch 410-1 and switch 410-2) coupled to low-pass filter 406.

[0070] When the quadrupole mass filter is being operated at the lower resonance frequency, low-pass filter 404, in-line between switches 408, may provide essentially full transmission of RF power at a fundamental frequency and progressively stronger attenuation of second, third, and higher order harmonics in the path to primary winding 320 of low-frequency transformer assembly 318. Further, as described above, switches 410 may be opened to disconnect RF amplifier 314 from high- frequency transformer assembly 324.

[0071] Conversely, when the quadrupole mass filter is being operated at the higher resonance frequency, low-pass filter 406, in-line between switches 410, may provide essentially full transmission of RF power at a (higher) fundamental frequency and progressively greater attenuation of second, third and higher order harmonics in the path to primary winding 326 of high-frequency transformer assembly 324.Likewise, switches 408 may be opened to disconnect RF amplifier 314 from low- frequency transformer assembly 318.

[0072] Additionally, low-pass filter 404 and / or low-pass filter 406 may further provide an impedance transformation function. For instance, RF amplifier 314 may be designed to drive a 50-ohm resistive load. Low-pass filter 404 and low-pass filter 406 may provide an impedance transformation from 50 ohms to 75 ohms to allow the RF power to be transmitted through 75-ohm coaxial cables to the 75-ohm input impedances of primary winding 320 and primary winding 326 when driven at the lower and higher resonant frequencies, respectively.

[0073] Additionally or alternatively, dual-frequency power system 308 may include one or more RF detector capacitors 412. The RF detector capacitors may sample an RF current that is rectified in an RF control circuit 414 to provide high precision and stable feedback for regulation of the RF magnitude applied to the quadrupoleelectrodes. An error signal (modulation) representative of a difference between the detected RF magnitude of the RF voltage and a command RF magnitude setting signal may be transmitted from the RF control circuit 414 to the RF amplifier. This error signal may full wave modulate the reference RF sine wave generated in a programmable RF generator 416, which may be configured to output the reference RF sine wave to RF amplifier 314. This modulated RF voltage may be amplified by RF amplifier 314 and used to drive one of low-frequency transformer assembly 318 or high-frequency transformer assembly 324.

[0074] Additionally or alternatively, RF control circuit 414 may provide a signal that is derived from a magnitude of a detected RF amplitude, which may be transmitted to a DC rod driver amplifier module that generates a differential DC voltage to provide m / z selection in the quadrupole. These DC voltages may further be filtered through RF blocking filters (not shown), and inserted at center taps of low- frequency transformer assembly 318. Further, a value of a capacitor 332 across the output of x-rod DC source 310 and y-rod DC source 312 may be chosen such that the capacitance of capacitor 332 creates a sufficiently low impedance that a suitably small fraction of the RF voltage at either output end of secondary winding 322 of low- frequency transformer assembly 318 appears across capacitor 332.

[0075] Switching circuit 316 may provide for relatively rapid switching between quadrupole operating frequencies, such as on the order of ten milliseconds or less. For example, dual-frequency power system 308 may include and / or be communicatively coupled to a controller (e.g., control module 256, controller 112, and / or any other suitable controller) connected to and / or in communication with RF generator 416 and configured to operate selectively in different operating modes corresponding to the operating frequencies. The controller may set RF generator 416 to output the low or high frequency (e.g., via RF amplifier 314) and set switching circuit 316 to connect RF amplifier 314 to low-frequency transformer assembly 318 or high-frequency transformer assembly 324 accordingly.

[0076] When switching between operating frequencies, RF amplifier 314 may be made to be zero by turning the RF frequency reference signal off. The RF voltage on the connected transformer circuit may be allowed to sufficiently decay away, the switches of switching circuit 316 are switched, and then RF amplifier 314 may be turned back on by outputting the new operating frequency from RF generator 416. The RF voltage magnitude and the DC rod electrode voltages delivered to thequadrupole m / z filter rod electrodes may equilibrate to appropriate values for desired m / z ions to be transmitted at the desired m / z resolution (transmission window width).

[0077] It is an advantage of the systems and methods taught herein that switching between high frequency and low frequency modes can be achieved rapidly without the need to use expensive high voltage supplies and electronic relay switches to switch taps on the output coil of a single transformer power system. By employing the switching circuit 316 and two tuned transformer assemblies, the switching circuit 316 can employ lower-cost RF-compatible relay switches that are designed to handle maximum voltages on the order of a few hundreds of volts as well as lower cost RF generators.

[0078] In some examples, a controller (e.g., controller 112, computing devices 206, etc.) may be configured to switch operating modes based on detecting a condition. For example, a detected condition may include a user providing input indicating a selected operating mode. Additionally or alternatively, the controller, mass analyzer, and / or mass spectrometer may be configured to determine the operating mode, for instance, based on detected ions in a particular m / z range (e.g., based on detecting ions in the m / z range of a current operating mode, based on a scan across both operating modes, etc.) and / or a lack of detecting ions in a particular m / z range (e.g., switching modes based on detecting ions below a threshold level in a 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 may provide an indication of an m / z range of ions to be expected.

[0079] One or more operations associated with a dual-frequency system for mass spectrometry may be performed by a control system in conjunction with an MS system (e.g., mass spectrometer 102, mass spectrometer system 204, an LC-MS system, a GC-MS system, or a CE-MS system). The control system may control and / or perform one or more operations described herein. FIG. 5 shows a functional diagram of an illustrative control system 500 (“system 500”). System 500 may be implemented entirely or in part 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 separate from but communicatively coupled to control module 256 and / or controller 112).

[0080] System 500 may include, without limitation, a memory 502 and a processor 504 selectively and communicatively coupled to one another. Memory 502 and processor 504 may each include or be implemented by hardware and / or software components (e.g., processors, memories, communication interfaces, instructions stored in memory for execution by the processors, etc.). Memory 502 and processor 504 may be distributed between multiple devices and / or multiple locations as may serve a particular implementation.

[0081] Memory 502 may maintain (e.g., store) executable data used by processor 504 to perform any of the operations described herein. For example, memory 502 may store instructions 506 that may 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 executable data instance. Memory 502 may also maintain any data acquired, received, generated, managed, used, and / or transmitted by processor 504.

[0082] Processor 504 is configured to perform (e.g., execute instructions 506 stored in memory 502 to perform) various processing operations described herein. It will be recognized that the operations and examples described herein are merely illustrative of the many different types of operations that may be performed by processor 504. In the description herein, any references to operations performed by system 500 may be understood to be performed by processor 504 of system 500. Furthermore, in the description herein, any operations performed by system 500 may be understood to include system 500 directing, commanding, or instructing another system or device to perform the operations.

[0083] In certain embodiments, one or more of the systems, components, and / or processes described herein may be implemented and / or performed by one or more appropriately 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-implemented instructions (e.g., software) embodied on at least one non-transitory computer-readable medium configured to perform one or more of the processes described herein. In particular, system components may be implemented on one physical computing device or may be implemented on more than one physical computing device. Accordingly, system components may include any number of computing devices, and may employ any of a number of computer operating systems.

[0084] In certain embodiments, one or more of the 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. In general, a processor (e.g., a microprocessor) receives instructions, from a non- transitory computer-readable medium, (e.g., a memory, etc.), and executes those instructions, thereby performing one or more processes, including one or more of the processes described herein. Such instructions may be stored and / or transmitted using any of a variety of known computer-readable media.

[0085] A computer-readable medium (also referred to as a processor-readable medium) includes any non-transitory medium that participates in providing data (e.g., instructions) that may be read by a computer (e.g., by a processor of a computer). Such a medium may take many forms, including, but not limited to, non-volatile media, and / or volatile media. Non-volatile media may include, for example, optical or magnetic disks and other persistent memory. Volatile media may include, for example, dynamic random access memory (“DRAM”), which typically constitutes a main memory. Common forms of computer-readable media include, for example, a disk, hard disk, magnetic tape, any other magnetic medium, a compact disc readonly memory (“CD-ROM”), a digital video disc (“DVD”), any other optical medium, random access memory (“RAM”), programmable read-only memory (“PROM”), electrically erasable programmable read-only memory (“EPROM”), FLASH- EEPROM, any other memory chip or cartridge, or any other tangible medium from which a computer can read.

[0086] FIG. 6 shows an illustrative computing device 600 that may be specifically configured to perform one or more of the processes described herein. As shown in FIG. 6, computing device 600 may include a communication interface 602, a processor 604, a storage device 606, and an input / output (“I / O”) module 608 communicatively connected one to another via a communication infrastructure 610. While an illustrative computing device 600 is shown in FIG. 6, the components illustrated in FIG. 6 are not intended to be limiting. Additional or alternative components may be used in other embodiments. Components of computing device 600 shown in FIG. 6 will now be described in additional detail.

[0087] Communication interface 602 may be configured to communicate with one or more computing devices. Examples of communication interface 602 include, without limitation, a wired network interface (such as a network interface card), awireless network interface (such as a wireless network interface card), a modem, an audio / video connection, and any other suitable interface.

[0088] Processor 604 generally represents any type or form of processing unit capable of processing data and / or interpreting, executing, and / or directing execution of one or more of the instructions, processes, and / or operations described herein. Processor 604 may perform operations by executing computer-executable instructions 612 (e.g., an application, software, code, and / or other executable data instance) stored in storage device 606.

[0089] Storage device 606 may include one or more data storage media, devices, or configurations and may employ any type, form, and combination of data storage media and / or device. For example, storage device 606 may include, but is not limited to, any combination of the non-volatile media and / or volatile media described herein. Electronic data, including data described herein, may be temporarily and / or permanently stored in storage device 606. For example, data representative of computer-executable instructions 612 configured to direct 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 combination thereof supportive of 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., touchscreen display), a receiver (e.g., an RF or infrared receiver), motion sensors, 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 display screen), one or more output drivers (e.g., display drivers), one or more audio speakers, and one or more audio drivers. In certain embodiments, I / O module 608 is configured to provide graphical data to a display for presentation to a user. The graphical data may be representative of one or more graphical user interfaces and / or any other graphical content as may serve 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] Fig. 7 depicts a flow chart 700 illustrating an example method for controlling a dual-frequency power system, in accordance with some embodiments of the present disclosure. While the flowchart depicts illustrative operations according to some embodiments, other embodiments may omit, add to, reorder, combine, and / or modify any of the operations shown in the flowcharts. In some implementations, one or more of the operations shown in the flowcharts may be performed by a controller such as controller 112, computing devices 206, etc.

[0094] The example method includes, at operation 702, detecting a condition for switching an operating mode of the dual-frequency power system from a first operating mode to a second operating mode. Operation 702 may be performed in any of the ways described herein.

[0095] The example method includes, at operation 704, causing, based on the detecting the condition, the dual-frequency power system to switch from operating in the first mode to operating in a second mode. Operation 704 may be performed in any of the ways described herein. For example, operation 704 may include causing a signal generator (e.g., an RF generator) of the dual-frequency power system to disconnect from a first transformer circuit configured to resonate at a first frequency and to supply a first transformed voltage based on the signal voltage to an output coupled to the multipole electrodes, setting a signal generator of the dual-frequency power system to switch from outputting a signal voltage at the first frequency to outputting the signal voltage at a second frequency, and causing the signal generator of the dual-frequency system to connect to a second transformer circuit configured to resonate at the second frequency and to supply a second transformed voltage based on the signal voltage to the output coupled to the multipole electrodes.

[0096] It will be recognized by those of ordinary skill in the art that while, in the preceding description, various illustrative embodiments have been described with reference to the accompanying drawings. It will, however, be evident that various modifications and changes may be made thereto, and additional embodiments may be implemented, without departing from the scope of the invention as set forth in the claims that follow. For example, certain features of one embodiment describedherein may be combined with or substituted for features of another embodiment described herein. The description and drawings are accordingly to be regarded in an illustrative rather than a restrictive sense.

[0097] For example, while the embodiments described include x-rod DC source 310 and y-rod DC source 312 configured to provide a differential DC voltage to set of electrodes 302, methods and systems described herein may be applied to any other suitable circuit topologies. For instance, a multi-filar topology configured to provide an AC voltage in addition to an RF drive voltage (e.g., for an ion trap or any other suitable multipole structure) may incorporate features of the systems described herein, such as switching circuit 316 (including any suitable modifications) configured to connect a power source to one of two transformer assemblies to provide a dualfrequency RF generation system. An example multi-filar topology that can be suitably modified to use the power systems taught herein can be found in U.S. Patent 6,844,547, the entire contents of which is incorporated herein by reference.

[0098] Advantages and features of the present disclosure can be further described by the following statements:

[0099] 1. An apparatus for performing mass spectrometry comprising: a set of multipole electrodes; an RF generator configured to selectively output an RF voltage at a first resonant frequency or at a second resonant frequency for driving 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 configured to supply a first voltage based on the RF voltage to an output coupled to the set of multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the set of multipole electrodes.

[0100] 2. The apparatus of any of the preceding statements, wherein the switching circuit includes a first low-pass network to filter power at harmonics of the first resonant frequency and a second low-pass network to filter power at harmonics of the second resonant frequency.

[0101] 3. The apparatus of any of the preceding statements, wherein the first low- pass network and the second low-pass network provide an impedance transformation between the RF generator and the output.

[0102] 4. The apparatus of any of the preceding statements, further comprising a controller connected to the RF generator and the switching circuit and configured to operate selectively in a first mode or a second mode, wherein: in the first mode, the controller sets the RF generator to output the RF voltage at the first resonant frequency, sets the switching circuit to connect the RF generator and the low- frequency transformer assembly, and sets 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.

[0103] 5. The apparatus of any of the preceding statements, further comprising a quadrupole mass filter that includes the set of multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a first mass-to-charge (m / z) range, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a second m / z range that is lower than the first m / z range.

[0104] 6. The apparatus of any of the preceding statements, further comprising a quadrupole mass filter that includes the set of multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z magnitude, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z resolution.

[0105] 7. The apparatus of any of the preceding statements, wherein the first resonant frequency is less than one-half of the second resonant frequency.

[0106] 8. The apparatus of any of the preceding statements, wherein the switching circuit is configured to switch connections between the high-frequency transformer assembly and the low-frequency transformer assembly in less than 10 milliseconds.

[0107] 9. The apparatus of any of the preceding statements, wherein the low- frequency transformer assembly and the high-frequency transformer assembly both comprise air-core transformers.

[0108] 10. The apparatus of any of the preceding statements, wherein the low- frequency transformer assembly comprises a split transformer having two halves, the apparatus further comprising a capacitor connected across both halves of the low- frequency transformer assembly.

[0109] 11. A dual-frequency power system to drive multipole electrodes, comprising: an RF generator configured to selectively output an RF voltage at a first resonant frequency or at 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 configured to supply a first voltage based on the RF voltage to an output coupled to the set of multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high- frequency transformer assembly configured to supply a second voltage based on the RF voltage to an output coupled to the set of multipole electrodes.

[0110] 12. The system of any of the preceding statements, wherein the switching circuit includes a first low-pass network to filter power at harmonics of the first resonant frequency and a second low-pass network to filter power at harmonics of the second resonant frequency.

[0111] 13. The system of any of the preceding statements, wherein the first low- pass network and the second low-pass network provide an impedance transformation between the RF generator and the output.

[0112] 14. The system of any of the preceding statements, further comprising a controller connected to the RF generator and the switching circuit and configured to operate selectively in a first mode or a second mode, wherein: in the first mode, the controller sets the RF generator to output the RF voltage at the first resonant frequency, sets the switching circuit to connect the RF generator and the low- frequency transformer assembly, and sets 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 resonantfrequency, 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.

[0113] 15. The system of any of the preceding statements, further comprising a quadrupole mass filter that includes the multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a first mass-to-charge (m / z) range, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a second m / z range that is lower than the first m / z range.

[0114] 16. The system of any of the preceding statements, further comprising a quadrupole mass filter that includes the multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z magnitude, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z resolution.

[0115] 17. The system of any of the preceding statements, wherein the first resonant frequency is less than one-half of the second resonant frequency.

[0116] 18. The system of any of the preceding statements, wherein the switching circuit is configured to switch connections between the high-frequency transformer assembly and the low-frequency transformer assembly in less than 10 milliseconds.

[0117] 19. The system of any of the preceding statements, wherein the low- frequency transformer assembly and the high-frequency transformer assembly both comprise air-core transformers.

[0118] 20. The system of any of the preceding statements, wherein the low- frequency transformer assembly comprises a split transformer having two halves, the system further comprising a capacitor connected across both halves of the low- frequency transformer assembly.

[0119] 21. A method for controlling a dual-frequency power system to drive multipole electrodes, the method comprising: detecting, while the dual-frequency power system is operating in a first mode, a condition; and causing, based on the detecting the condition, the dual-frequency power system to switch from operating in the first mode to operating in a second mode, the causing comprising: causing an RF generator of the dual-frequency power system to disconnect from a first transformer assembly configured to supply a first voltage based on an RF voltage to an outputcoupled to the multipole electrodes when the RF generator outputs the RF voltage at a first resonant frequency; setting the RF generator of the dual-frequency power system to switch from outputting the RF voltage at the first resonant frequency to outputting the RF voltage at a second resonant frequency; and causing the RF generator of the dual-frequency power system to connect to a second transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the multipole electrodes.

Claims

CLAIMSWhat is claimed is:

1. An apparatus for performing mass spectrometry comprising: a set of multipole electrodes; an RF generator configured to selectively output an RF voltage at a first resonant frequency or at a second resonant frequency for driving 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 configured to supply a first voltage based on the RF voltage to an output coupled to the set of multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the set of multipole electrodes.

2. The apparatus of claim 1 , wherein the switching circuit includes a first low-pass network to filter power at harmonics of the first resonant frequency and a second low-pass network to filter power at harmonics of the second resonant frequency.

3. The apparatus of claim 2, wherein the first low-pass network and the second low-pass network provide an 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 operate selectively in a first mode or a second mode, wherein: in the first mode, the controller sets the RF generator to output the RF voltage at the first resonant frequency, sets the switching circuit to connect the RF generatorand the low-frequency transformer assembly, and sets 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 that includes the set of multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a first mass-to-charge (m / z) range, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a second m / z range that is lower than the first m / z range.

6. The apparatus of claim 1 , further comprising a quadrupole mass filter that includes the set of multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z magnitude, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z resolution.

7. The apparatus of claim 1 , wherein the first resonant frequency is less than one-half of the second resonant frequency.

8. The apparatus of claim 1 , wherein the switching circuit is configured to switch connections between the high-frequency transformer assembly and the low- frequency transformer assembly in less than 10 milliseconds.

9. The apparatus of claim 1 , wherein the low-frequency transformer assembly and the high-frequency transformer assembly both comprise air-core transformers.

10. The apparatus of claim 1 , wherein the low-frequency transformer assembly comprises a split transformer having two halves, the apparatus further comprising a capacitor connected across both halves of the low-frequency transformer assembly.

11. A dual-frequency power system to drive multipole electrodes, comprising: an RF generator configured to selectively output an RF voltage at a first resonant frequency or at 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 configured to supply a first voltage based on the RF voltage to an output coupled to the multipole electrodes, or the high-frequency transformer assembly when the RF generator outputs the RF voltage at the second resonant frequency, the high-frequency transformer assembly configured to supply a second voltage based on the RF voltage to an output coupled to the multipole electrodes.

12. The system of claim 11 , wherein the switching circuit includes a first low-pass network to filter power at harmonics of the first resonant frequency and a second low-pass network to filter power at harmonics of the second resonant frequency.

13. The system of claim 12, wherein the first low-pass network and the second low-pass network provide an 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 operate selectively in a first mode or a second mode, wherein:in the first mode, the controller sets the RF generator to output the RF voltage at the first resonant frequency, sets the switching circuit to connect the RF generator and the low-frequency transformer assembly, and sets 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 that includes the multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a first mass-to-charge (m / z) range, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a second m / z range that is lower than the first m / z range.

16. The system of claim 11 , further comprising a quadrupole mass filter that includes the multipole electrodes, and wherein the first voltage at the first resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z magnitude, and wherein the second voltage at the second resonant frequency enables the quadrupole mass filter to filter ions over a threshold m / z resolution.

17. The system of claim 11 , wherein the first resonant frequency is less than one-half of the second resonant frequency.

18. The system of claim 11 , wherein the switching circuit is configured to switch connections between the high-frequency transformer assembly and the low- frequency transformer assembly in less than 10 milliseconds.

19. The system of claim 11 , wherein the low-frequency transformer assembly and the high-frequency transformer assembly both comprise air-core transformers.

20. The system of claim 11 , wherein the low-frequency transformer assembly comprises a split transformer having two halves, the system further comprising a capacitor connected across both halves of the low-frequency transformer assembly.

21. A method for controlling a dual-frequency power system to drive multipole electrodes, the method comprising: detecting, while the dual-frequency power system is operating in a first mode, a condition; and causing, based on the detecting the condition, the dual-frequency power system to switch from operating in the first mode to operating in a second mode, the causing comprising: causing an RF generator of the dual-frequency power system to disconnect from a first transformer assembly configured to supply a first voltage based on an RF voltage to an output coupled to the multipole electrodes when the RF generator outputs the RF voltage at a first resonant frequency; setting the RF generator of the dual-frequency power system to switch from outputting the RF voltage at the first resonant frequency to outputting the RF voltage at a second resonant frequency; and causing the RF generator of the dual-frequency power system to connect to a second transformer assembly configured to supply a second voltage based on the RF voltage to the output coupled to the multipole electrodes.

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