Calibration of mirrored current-based mass analyzers included in mass spectrometers

Abstract

The invention relates to calibration of a mirror current-based mass analyzer included in a mass spectrometer. An exemplary method includes determining a mass spectrum including one or more peaks representing an intensity as a function of m / z of a first ion population across a range of mass-to-charge ratio (m / z) values based on a mass analysis performed by an electron multiplier-based mass analyzer on the first ion population generated from a sample; determining a total ion count of the first ion population and a peak ion count associated with a peak located at a particular m / z value based on the mass spectrum; determining a total ion count of a second ion population generated from the sample and injected into a mirror current-based mass analyzer for mass analysis based on the total ion count of the first ion population and the peak ion count; and setting a calibration parameter for the mirror current-based mass analyzer based on the total ion count of the second ion population.

Description

Background Art

[0001] Automatic gain control is useful for image current based mass analyzers included in mass spectrometers (e.g., orbital electrostatic trap mass analyzers such as the Orbitrap mass analyzer manufactured and sold by Thermo Fisher Scientific, Inc., Waltham, MA). TM It is important to ensure mass accuracy and precision in a mass analyzer based on image current. This is because image current-based mass analyzers are susceptible to space charge effects and therefore require the injection of a reproducible number of ions, provided by automatic gain control. Unfortunately, due to chemical noise, ion transfer inefficiencies, spray instabilities, and / or other factors, it can be difficult to accurately determine the total number of ions actually injected into an image current-based mass analyzer. Summary of the Invention

[0002] The following description presents a simplified overview of one or more aspects of the systems and methods described herein. This summary is not an extensive overview of all covered aspects and is neither intended to identify key or critical elements of all aspects nor to delineate the scope of any or all aspects. Its sole purpose is to present one or more aspects of the systems and methods described herein as a prelude to the detailed description presented below.

[0003] In some exemplary embodiments, a system includes: a memory that stores instructions; and one or more processors that are communicatively coupled to the memory and configured to execute the instructions to perform a process including the following steps: determining a mass spectrum including one or more peaks based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, the one or more peaks representing intensity as a function of m / z of the first ion population across a range of mass-to-charge ratio (m / z) values; determining, based on the mass spectrum, a total ion count of the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a specific m / z value within the range of m / z values; determining, based on the total ion count and the peak ion count of the first ion population, a total ion count of a second ion population generated from the sample and injected into the image current-based mass analyzer for mass analysis; and setting calibration parameters for the image current-based mass analyzer based on the total ion count of the second ion population.

[0004] In some exemplary embodiments, a system includes: an electron multiplier-based mass analyzer configured to perform mass analysis on a first ion population generated from a sample; a controller configured to determine, based on the mass analysis performed by the electron multiplier-based mass analyzer, a mass spectrum including one or more peaks representing intensity as a function of m / z for the first ion population across a range of m / z values, and to determine, based on the mass spectrum, a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values; and an image current-based mass analyzer configured to perform mass analysis on a first ion population generated from a sample; a controller configured to determine, based on the mass analysis performed by the electron multiplier-based mass analyzer, a mass spectrum including one or more peaks representing intensity as a function of m / z for the first ion population across a range of m / z values; and a controller configured to determine, based on the mass spectrum, a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values. The analyzer is configured to perform mass analysis on a second ion population generated from the sample after the mass analysis performed by the electron multiplier-based mass analyzer; wherein the controller is further configured to: determine an additional mass spectrum including one or more peaks representing intensity as a function of m / z of the second ion population across the range of m / z values ​​based on the mass analysis performed by the image current-based mass analyzer on the second ion population; determine additional peak ion counts associated with the peak at the particular m / z value within the range of m / z values ​​based on the additional mass spectrum; and determine a total ion count for the second ion population based on the total ion count of the first ion population, the peak ion count, and the additional peak ion counts.

[0005] In some exemplary embodiments, a method includes: determining a mass spectrum including one or more peaks based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, the one or more peaks representing intensity as a function of m / z for the first ion population across a range of m / z values; determining a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a specific m / z value within the range of m / z values ​​based on the mass spectrum; determining a total ion count for a second ion population generated from the sample and injected into the image current-based mass analyzer for mass analysis based on the total ion count and the peak ion count for the first ion population; and setting calibration parameters for the image current-based mass analyzer based on the total ion count for the second ion population.

[0006] In some exemplary embodiments, a non-transitory computer-readable medium stores instructions that, when executed, direct a processor of a computing device to perform a process comprising the following steps: determining a mass spectrum including one or more peaks based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, the one or more peaks representing intensity as a function of m / z of the first ion population across a range of m / z values; determining, based on the mass spectrum, a total ion count of the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a specific m / z value within the range of m / z values; determining, based on the total ion count and the peak ion count of the first ion population, a total ion count of a second ion population generated from the sample and injected into the image current-based mass analyzer for mass analysis; and setting calibration parameters for the image current-based mass analyzer based on the total ion count of the second ion population. BRIEF DESCRIPTION OF THE DRAWINGS

[0007] The accompanying drawings illustrate various embodiments and are part of the specification. The illustrated embodiments are examples only and do not limit the scope of the present disclosure. Throughout the drawings, the same or similar reference numerals represent the same or similar elements.

[0008] Figure 1 An illustrative configuration is shown in which a calibration management system is communicatively coupled with a mass spectrometer.

[0009] Figure 2 Illustrative components of a calibration management system are shown.

[0010] Figure 3 A functional diagram of an exemplary embodiment of a mass spectrometer is shown.

[0011] Figure 4 An illustrative method of calibrating an image current-based mass analyzer included in a mass spectrometer is shown.

[0012] Figure 5 An exemplary mass spectrum of ion populations mass analyzed by an electron multiplier based mass analyzer is shown.

[0013] Figure 6 Illustrative modules of a calibration management system that can be used to determine calibration parameters for an image current based mass analyzer are shown.

[0014] Figure 7A and Figure 7B A mass spectrum that may be determined by a calibration management system is shown.

[0015] Figure 8A and Figure 8B A mass spectrum that may be determined by a calibration management system is shown.

[0016] Figure 9 An exemplary computing device is shown that may be specifically configured to perform one or more of the operations, methods, and processes described herein. DETAILED DESCRIPTION

[0017] The present invention relates to a system and method for calibrating an image current-based mass analyzer included in a mass spectrometer. For example, as described herein, a calibration management system can determine, based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, a mass spectrum comprising one or more peaks representing intensities as a function of mass-to-charge ratio (m / z) values ​​of the first ion population; determine, based on the mass spectrum, a total ion count of the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values; determine, based on the total ion count and the peak ion count of the first ion population, a total ion count of a second ion population generated from the sample and injected into the image current-based mass analyzer for mass analysis; and set calibration parameters for the image current-based mass analyzer based on the total ion count of the second ion population.

[0018] As used herein, "calibrating" an image current-based mass analyzer refers to setting calibration parameters for the image current-based mass analyzer. "Calibration parameters" refers to any settings, coefficients, and / or other parameters used to convert or map the frequency of ion oscillations within an image current-based mass analyzer to m / z. As described herein, the setting of appropriate calibration parameters depends on the total ion count of ions injected into the image current-based mass analyzer for mass analysis.

[0019] As used herein, "ion population" may refer to a single or multiple charged particles having an m / z within a specified range. Thus, "ion count" (e.g., total ion count and peak ion count referred to herein) may refer to a count of actual ions or a measure of the total charge associated with actual ions.

[0020] The systems and methods described herein can determine an accurate total ion count for ion populations within an image current-based mass analyzer. This can allow for accurate calibration of the image current-based mass analyzer, which can ensure accurate mapping of frequency to m / z for ion populations mass analyzed by the image current-based mass analyzer.

[0021] Figure 1An exemplary configuration 100 is shown in which a calibration management system 102 is communicatively coupled to a mass spectrometer 104. As shown, the mass spectrometer 104 includes an electron multiplier-based mass analyzer 106 and an image current-based mass analyzer 108. The mass spectrometer 104 may include additional or alternative components (e.g., one or more additional mass analyzers) as may serve a particular embodiment. An exemplary embodiment of the mass spectrometer 104 includes an Orbitrap 500 manufactured and sold by Thermo Fisher Scientific, Inc., Waltham, MA. TM Tribrid TM Mass spectrometer.

[0022] The electron multiplier-based mass analyzer 106 may be implemented by any type of mass analyzer configured to detect ions using electron multiplication and / or any other type of single charge detection capability. For example, the electron multiplier-based mass analyzer 106 may be implemented by a mass analyzer configured to detect ions using electron multiplication, such as a linear ion trap, a time-of-flight mass analyzer, a combination of a scintillator and a photomultiplier tube, or the like.

[0023] The image current based mass analyzer 108 can be implemented by any type of mass analyzer that measures the frequency at which ions oscillate in the presence of a magnetic field or an electrostatic field. For example, the image current based mass analyzer 108 can be implemented by a Fourier transform ion cyclotron resonance (FT-ICR) mass analyzer or an electrostatic trap mass analyzer (such as an orbital electrostatic trap mass analyzer, such as an Orbitrap). TM mass analyzer) to achieve this.

[0024] The electron multiplier-based mass analyzer 106 and the image current-based mass analyzer 108 can be used together in any suitable manner. For example, in some embodiments (e.g., where the mass spectrometer 104 is an Orbitrap TM Tribrid TM A mass analyzer 106 based on an electron multiplier can be used to measure the ion flux and determine an analysis injection time that will provide an appropriate number of ions for analysis by the image current based mass analyzer 108.

[0025] The calibration management system 102 can be configured to perform one or more calibration operations with respect to the mass spectrometer 104. For example, the calibration management system 102 can be configured to set calibration parameters for the image current-based mass analyzer 108. As described above, the calibration parameters for the image current-based mass analyzer 108 refer to any settings, coefficients, and / or other parameters used to convert or map frequency (e.g., the frequency at which ions oscillate within the image current-based mass analyzer) to m / z.

[0026] As described herein, the setting of appropriate calibration parameters for the image current-based mass analyzer 108 depends on the total ion count of ions injected into the image current-based mass analyzer 108 for mass analysis. For example, an exemplary calibration function for converting frequency to m / z can be represented by the following formula: m / z = K / f^2, where K is a calibration factor that can be set by the calibration management system 102, and f is the observed frequency. The calibration factor K depends on the total ion population within the image current-based mass analyzer 108. For example, the greater the number of ions within the image current-based mass analyzer 108, the lower the frequency of ion motion at any m / z. Other calibration functions (e.g., with higher-order terms) can be used to convert frequency to m / z, as may be suitable for a particular embodiment. For example, another calibration function for converting frequency to m / z can be represented by the following formula: m / z = A / f^2 + B / f^4, where A and B are calibration factors that can be set by the calibration management system 102, and f is the observed frequency.

[0027] Calibration management system 102 can be implemented by any combination of one or more computing devices. For example, calibration management system 102 can be implemented by a controller included in a mass spectrometer, one or more computing devices configured to be communicatively coupled to mass spectrometer 104, and / or any other local and / or remote computing devices as may serve a particular embodiment.

[0028] Figure 2 Illustrative components of the calibration management system 102 are shown. For example, the calibration management system 102 may include, but is not limited to, a storage facility 202 and a processing facility 204 that are selectively and communicatively coupled to each other. Facilities 202 and 204 can each include or be implemented by hardware components and / or software components (e.g., a processor, memory, a communication interface, instructions stored in the memory for execution by the processor, etc.). In some examples, facilities 202 and 204 can be distributed across multiple devices and / or multiple locations, as may be required for a particular embodiment. For example, facility 202 can be distributed across one or more local computing resources and one or more remote computing resources that are communicatively coupled to the local computing resources via a network.

[0029] The storage facility 202 may maintain (e.g., store) executable data used by the processing facility 204 to perform any of the operations described herein. For example, the storage facility 202 may store instructions 206 that may be executed by the processing facility 204 to perform any of the operations described herein. The instructions 206 may be implemented by any suitable application, software, code, and / or other executable data instances. The storage facility 202 may also maintain any data collected, received, generated, managed, used, and / or transmitted by the processing facility 204.

[0030] The processing facility 204 can be configured to perform (e.g., execute instructions 206 stored in the storage facility 202 to perform) the various processing operations described herein. It will be appreciated that the operations and examples described herein are merely illustrative of the many different types of operations that can be performed by the processing facility 204. In the description herein, any reference to an operation performed by the calibration management system 102 can be understood to be performed by the processing facility 204 of the calibration management system 102. Furthermore, in the description herein, any operation performed by the calibration management system 102 can include the calibration management system 102 directing or instructing another computing system, device, or apparatus to perform an operation.

[0031] Figure 3 A functional diagram of an exemplary embodiment 300 of the mass spectrometer 104 is shown. As shown, the embodiment 300 includes an ion source 302, a mass filter 304, an ion storage 306, an electron multiplier-based mass analyzer 106, an image current-based mass analyzer 108, and a controller 308. The embodiment 300 may also include any additional or alternative components not shown that may be suitable for a particular embodiment (e.g., ion optics, lenses, filters, ion storage devices, ion mobility analyzers, collision cells, ion flux monitors, etc.).

[0032] The ion source 302 is configured to generate ions from a sample and deliver the ions in the ion stream 310-1 to the mass filter 304. The sample can be generated in any suitable manner and injected using a liquid chromatography procedure. The ion source 302 can use any suitable ionization technique, including but not limited to electron ionization, chemical ionization, matrix-assisted laser desorption / ionization, electrospray ionization, atmospheric pressure chemical ionization, atmospheric pressure photoionization, inductively coupled plasma, etc. The ion source 302 may include various components for generating ions from the sample and delivering the ions to the mass filter 304.

[0033] The mass filter 304 can be implemented by any suitable mass filter, such as a linear multipole mass filter (e.g., a quadrupole mass filter). The mass filter 304 can filter the ion stream 310-1 to selectively transfer ions within a selected m / z range in the ion stream 310-2 to the ion storage 306. Although the embodiment 300 includes the mass filter 304, alternative embodiments can omit the mass filter 304. In these alternative embodiments, the ion stream 310-1 can be provided directly from the ion source 302 to the ion storage 306.

[0034] Ion storage 306 is a device configured to accumulate ions included in ion stream 310-2 over an accumulation time. As used herein, "accumulation time" refers to the duration that ions generated by ion source 302 accumulate in ion storage 306 before being released and transferred to mass analyzer 106 and / or 108. The accumulation time may also be referred to as ion injection time or ion fill time. In some examples, ion storage 306 is an ion storage device configured to buffer downstream processes (such as mass analysis), thereby improving acquisition speed and instrument sensitivity. In some examples, ion storage 306 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 octopole ion guide, etc.), a linear quadrupole ion trap, a three-dimensional quadrupole ion trap, a cylindrical ion trap, a toroidal ion trap, an orbital electrostatic trap, a Kingdon trap, and similar ion traps. In some examples, ion storage 306 takes the form of a curved trap (also known as a C-trap) of the type used with orbital electrostatic trap mass spectrometers. In some examples, ion storage 306 may be omitted from embodiment 300. In these examples, the electron multiplier-based mass analyzer 106 may serve as an ion store for the image current-based mass analyzer 108 .

[0035] In some examples, ion storage 306 is a collision cell located upstream of mass analyzers 106 and 108. As used herein, the term "collision cell" can refer to any device arranged to produce product ions via a controlled dissociation process or an ion-ion reaction process, and is not limited to devices for collision-activated dissociation. For example, the collision cell can be configured to fragment ions using collision-induced dissociation (CID), electron transfer dissociation (ETD), electron capture dissociation (ECD), photoinduced dissociation (PID), surface-induced dissociation (SID), etc.

[0036] The accumulation of ions in the ion storage 306 can be adjusted by automatic gain control and / or any other system to achieve the target ion population in the ion storage 306, and therefore achieve the target signal density. The accumulation of ions can be adjusted in any suitable manner. In some examples, the accumulation of ions in the ion storage 306 can be adjusted by a gate device (not shown) that transmits or blocks the ion flow 310-2. The gate can be opened for a given amount of time to measure the appropriate number of ions, and then closed. The accumulated ions can then be transferred from the ion storage 306 to one or both of the mass analyzers 106 and 108 in the ion flow 312. The gate device can also be used to regulate the transmission of the ion flow 310-2. It will be appreciated that other techniques for regulating ion accumulation can be used.

[0037] The mass analyzers 106 and 108 are configured to perform mass analysis on the ion populations, as described herein. In some examples, the mass analyzers 106 and 108 can each include an ion detector configured to detect ions at each of a plurality of different m / z values ​​and responsively generate an electrical signal representing the intensity of the ions. The electrical signal can be transmitted to the controller 308 for processing, such as constructing a mass spectrum of the detected ions. For example, the mass analyzers 106 and 108 can each generate or provide data that can be used by the controller 308 to construct a mass spectrum.

[0038] As used herein, "mass spectrum" or "spectrum" refers to a plot of ion intensity as a function of the m / z of the ions. As used herein, "intensity" or "signal intensity" refers to the response of the ion detectors included in mass analyzers 106 and 108 and can represent absolute abundance, relative abundance, ion counts, intensity, relative intensity, ion current, or any other suitable measure of ion detection.

[0039] The controller 308 may implement some or all of the functionality performed by the calibration management system 102. For example, the controller 308 may be configured to control the operation of various hardware components included in the ion source 302, the mass filter 304, the ion storage 306, and the mass analyzers 106 and 108. To illustrate, the controller 308 may be configured to control the accumulation time of the ion storage 306, control the oscillating voltage power supply and / or the DC power supply to supply RF voltage and / or DC voltage to the mass analyzers 106 and 108, adjust the values ​​of the RF voltage and DC voltage to select a valid m / z (including a mass tolerance window) for analysis, and adjust the sensitivity of ion detection performed by the mass analyzers 106 and 108 (e.g., by adjusting detector gain).

[0040] Controller 308 may also include and / or provide a user interface that is configured to enable interaction between a user and controller 308. A user may interact with controller 308 via the user interface through tactile, visual, auditory, and / or other sensory types of communication. For example, the user interface may include a display device (e.g., a liquid crystal display (LCD) display screen, a touch screen, etc.) for displaying information (e.g., a mass spectrum, notifications, etc.) to the user. The user interface may also include an input device (e.g., a keyboard, a mouse, a touch screen device, etc.) that allows the user to provide input to controller 308. In other examples, the display device and / or input device may be separated from controller 308 but communicatively coupled to the controller. For example, the display device and input device may be included in a computer (e.g., a desktop computer, a laptop computer, a mobile device, etc.) that is communicatively connected to controller 308 through a wired connection (e.g., through one or more cables) and / or a wireless connection (e.g., Wi-Fi, Bluetooth, near field communication, etc.).

[0041] Controller 308 may include any suitable hardware (eg, processor, circuitry, etc.) and / or software as may serve a particular implementation. Figure 3 Controller 308 is shown included in embodiment 300, but controller 308 may alternatively be implemented in a manner that is completely or partially separate from embodiment 300, such as by a computing device that is communicatively coupled to embodiment 300 via 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.).

[0042] The methods, systems, and devices described herein can be operated as part of or in conjunction with embodiment 300 described herein and / or in conjunction with any other suitable mass spectrometer or mass spectrometry system, including a combined separation-mass spectrometry system, such as a liquid chromatography-mass spectrometry system (LC-MS), a high performance liquid chromatography-mass spectrometry system (HPLC-MS), a gas chromatography-mass spectrometry system (GC-MS), a capillary electrophoresis-mass spectrometry system (CE-MS), or an ion mobility system (IM-MS). The methods, systems, and devices described herein can also be operated in conjunction with a continuous flow sample source, such as flow infusion mass spectrometry (FI-MS), in which the analyte is injected into a solvent without separation in a column and enters the mass spectrometer.

[0043] Various factors may affect the ability to accurately determine the total number of ions actually injected into the image current based mass analyzer 108 .

[0044] For example, the image current-based mass analyzer 108 may not be able to detect chemical noise that falls below the detection threshold of the image current-based mass analyzer 108. This chemical noise is also referred to as dark ions (or dark ion current or dark ion signal) and can originate from various sources, such as intrinsic sample heterogeneity, solvent noise, residual gas, contamination on the sample or instrument surfaces, electronic noise, etc. Chemical noise is typically below the detection threshold of the image current-based mass analyzer 108 but contributes to the total ion count of ions in the image current-based mass analyzer 108.

[0045] Ion transfer inefficiency may also affect the total ion count of ions in the image current-based mass analyzer 108. Ion transfer inefficiency may refer to ion losses that may occur when ions are injected into the image current-based mass analyzer 108 for mass analysis. In some configurations, this ion loss may be due to saturation of the ion storage 306 (e.g., a C-trap) that may occur during the ion transfer process.

[0046] To illustrate, as mentioned, the electron multiplier-based mass analyzer 106 can be used to measure the ion flux of the ion current 312 (i.e., the rate at which ions will be injected into the image current-based mass analyzer 108) and determine an analysis injection time that will provide an appropriate number of ions for analysis by the image current-based mass analyzer 108. To this end, during a pre-scan operation prior to an acquisition to be performed by the image current-based mass analyzer 108, a first ion population generated from a sample may be accumulated in the ion store 306 and subsequently injected into the electron multiplier-based mass analyzer 106.

[0047] Based on the mass analysis performed on the first ion population by the electron multiplier-based mass analyzer 106, a total ion count for the first ion population can be determined. Based on the injection time into the ion storage 306 and the total ion count for the first ion population, the ion flux of the ion stream 312 can be determined. If the ion flux is, for example, 50k ions / millisecond, and it is desired to inject 500k ions into the image current-based mass analyzer 108, the ion storage 306 can inject ions into the image current-based mass analyzer 108 for 10 milliseconds. However, due to spray instabilities and ion transfer inefficiencies, this may not result in exactly 500k ions being injected into the image current-based mass analyzer 108.

[0048] As described herein, the calibration management system 102 may consider various factors that affect the measurement of the total ion count and determine the accurate total ion count within the image current based mass analyzer 108. This may allow the calibration management system 102 to accurately calibrate the image current based mass analyzer 108.

[0049] For example, Figure 4 An exemplary method 400 for calibrating an image current based mass analyzer included in a mass spectrometer is shown. Figure 4 Exemplary operations according to one embodiment are shown, but other embodiments may omit, add to, reorder, and / or modify Figure 4 Any of the actions shown. Figure 4 One or more of the illustrated operations may be performed by the calibration management system 102 , one or more of any components included therein, and / or any implementation thereof.

[0050] At operation 402, the calibration management system 102 may determine, based on mass analysis performed by an electron multiplier-based mass analyzer (e.g., the electron multiplier-based mass analyzer 106) on a first ion population generated from a sample, a mass spectrum comprising one or more peaks representing intensities as a function of m / z for the first ion population across a range of m / z values. This may be performed in any suitable manner.

[0051] Figure 5 An exemplary mass spectrum 500 of a first ion population mass analyzed by an electron multiplier-based mass analyzer is shown. As shown, the mass spectrum 500 may include multiple peaks 502 (eg, peaks 502-1 through 502-4). The intensity of each peak represents the number of ions at a particular m / z value.

[0052] Return to Figure 4 At operation 404 , the calibration management system 102 may determine, based on the mass spectrum, a total ion count of the first ion population across a range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values.

[0053] To illustrate, relative to Figure 5 In some examples, the range of m / z values ​​may include all m / z values ​​included in the mass spectrum. Alternatively, as will be described below, the range of m / z values ​​may include a subset of the m / z values ​​included in the mass spectrum.

[0054] Calibration management system 102 can determine the total ion count across a range of m / z values ​​in any suitable manner. For example, calibration management system 102 can sum the intensity values ​​for each peak included in the mass spectrum and determine the total ion count based on the summed intensity values.

[0055] Likewise, the calibration management system 102 can determine the peak ion count in any suitable manner. For example, the calibration management system 102 can identify the peak with the highest intensity compared to all other peaks included in the mass spectrum and determine the peak ion count based on the intensity of the peak. Figure 5In the example of , calibration management system 102 can determine that peak 502-2 has the highest intensity and determine the peak ion count based on the intensity of peak 502-2. Alternatively, calibration management system 102 can determine the peak ion count by summing multiple peaks and / or using the peak at a particular m / z value, even if that peak is not the most intense peak in the mass spectrum.

[0056] Because the mass analyzer based on an electron multiplier uses electron multiplication to detect ions, the mass analyzer based on an electron multiplier is able to detect chemical noise that may be present in the first ion population. For example, in some examples, the mass analyzer based on an electron multiplier can have a sufficiently high sensitivity so that it can detect a single ion. In this way, the total ion count and the peak ion count associated with the first ion quantity determined by the calibration management system 102 both take into account the chemical noise. In other words, the total ion count and the peak ion count associated with the first ion quantity determined by the calibration management system 102 both include counts of dark ions associated with the chemical noise.

[0057] In some examples, operations 402 and 404 can be performed during a pre-scan operation prior to injecting the second ion population generated from the sample into the image current-based mass analyzer for mass analysis. The pre-scan can be performed before each acquisition event performed by the image current-based mass analyzer and / or at any other suitable interval that may serve a particular embodiment (e.g., every N seconds, every N acquisitions, etc.).

[0058] At operation 406, the calibration management system 102 may determine a total ion count for a second ion population generated from the sample and injected into an image current-based mass analyzer (e.g., image current-based mass analyzer 108) for mass analysis based on the total ion count and peak ion count of the first ion population as determined at operation 404. Operation 406 may be performed in any suitable manner. For example, the calibration management system 102 may determine the total ion count for the second ion population using a ratio of the peak ion count to the total ion count for the first ion population. An example of how the calibration management system 102 may determine the total ion count for the second ion population based on the total ion count and peak ion count for the first ion population is provided below.

[0059] At operation 408, the calibration management system 102 may set calibration parameters for the image current-based mass analyzer based on the total ion count of the second ion population injected into the image current-based mass analyzer. This may be performed in any suitable manner. For example, the calibration management system 102 may use the total ion count of the second ion population to set an appropriate value for K in the equation m / z=K / f^2, which represents an exemplary calibration function that can be used to convert from frequency to m / z. The calibration parameters may be used to convert frequency to m / z for the second ion population and / or subsequent ion populations that may be mass analyzed by the image current-based mass analyzer.

[0060] Figure 6 Illustrative modules of the calibration management system 102 that can be used to determine calibration parameters for an image current-based mass analyzer are shown. As shown, the calibration management system 102 may include a total ion count determination module 602 and a calibration parameter generation module 604. Each of these modules may be implemented by any suitable combination of hardware and / or software (e.g., by the processing facility 204).

[0061] As shown, the total ion count determination module 602 may receive data representing a total ion count for a first ion population injected into the electron multiplier-based mass analyzer and a peak ion count associated with the first ion population injected into the electron multiplier-based mass analyzer, as determined in operation 404. As described above, these ion counts may be determined during a pre-scan operation performed using the electron multiplier-based mass analyzer.

[0062] As shown, the total ion count determination module 602 may also receive data representing a peak ion count associated with the image current-based mass analyzer. This peak ion count may be for a second ion population injected into the image current-based mass analyzer during a mass spectrometry acquisition operation performed after the pre-scan operation.

[0063] To illustrate, after a pre-scan operation in which a total ion count of a first ion population injected into an electron multiplier-based mass analyzer and a peak ion count associated with the first ion population injected into the electron multiplier-based mass analyzer are determined, a mass spectrometry acquisition operation can be performed using an image current-based mass analyzer. During the mass spectrometry acquisition operation, a second ion population generated from the same sample used for the pre-scan operation is injected into the image current-based mass analyzer. The injection can be performed under the direction of the calibration management system 102, the controller 308, and / or any other component.

[0064] The calibration management system 102 can determine, based on mass analysis of the second ion population performed by the image current-based mass analyzer, a mass spectrum comprising one or more peaks representing intensities as a function of m / z for the second ion population across a range of m / z values. The mass spectrum can be determined by the calibration management system 102 in any suitable manner.

[0065] To illustrate, Figure 7A and Figure 7B 5 and 700, respectively, are shown as mass spectra that may be determined by the calibration management system 102. Figure 5 The mass spectra shown are the same and are for a first ion population injected into an electron multiplier based mass analyzer. Mass spectrum 700 is for a second ion population injected into an image current based mass analyzer. 7A to 7B are depicted as vertically aligned with each other to convey that they all correspond to the same range of m / z values.

[0066] Based on mass spectrum 700, calibration management system 102 can determine a peak ion count associated with a peak located at the same m / z value as the peak ion count determined for the first ion population injected into the electron multiplier-based mass analyzer. For example, as depicted by dashed line 704, peak 502-2 and peak 702-2 are both located at the same m / z value. Therefore, calibration management system 102 can determine a peak ion count associated with peak 702-2.

[0067] Peak 702-2 is affected by both chemical noise and any transfer efficiency or spray stability issues that may be associated with injecting the second ion population into the image current based mass analyzer. Thus, the ratio of the peak ion count associated with peak 702-2 to the total ion counts for the second ion population injected into the image current based mass analyzer is the same as the ratio of the peak ion count associated with peak 502-2 to the total ion counts for the first ion population injected into the electron multiplier based mass analyzer. Thus, again referring to Figure 6 , the total ion count determination module 602 may determine the total ion count of the second ion population injected into the image current-based mass analyzer according to the following formula:

[0068] T IC =P IC *(T EM / P EM ).

[0069] In this formula, T IC represents the total ion count of the second ion population injected into the image current-based mass analyzer, P ICrepresents the peak ion count associated with peak 702-2 (which is a peak included in the mass spectrum of the second ion population injected into the image current-based mass analyzer), T EM represents the total ion counts of the first ion population injected into the electron multiplier-based mass analyzer, and P EM 502 - 502 represents the peak ion count associated with peak 502 - 2 , which is the peak included in the mass spectrum of the first ion population injected into the electron multiplier-based mass analyzer.

[0070] like Figure 6 As shown, the calibration parameter generation module 604 may receive data representing the total ion counts of the second ion population injected into the image current based mass analyzer (eg, T IC ), and based on this data, generates calibration parameters for the image current-based mass analyzer. This can be performed in any suitable manner. For example, the calibration parameter generation module 604 can maintain or otherwise access a relationship table that specifies the relationship between total ion count values ​​and calibration parameters and generate calibration parameters based on this table. For another example, the calibration parameter generation module 604 can generate calibration parameters based on a formula that specifies the calibration parameters as a function of the total ion count.

[0071] exist 7A to 7B In the example shown, the total ion count for the second ion population injected into the image current-based mass analyzer is for all ions across the entire range of m / z values ​​of the mass spectrum. Thus, the total ion count for the second ion population is based on the peak ion counts associated with peaks 502-2 and 702-2 at the same m / z value.

[0072] In some alternative examples, the calibration management system 102 can determine the total ion counts for the second ion population within multiple sub-ranges of m / z values ​​of the mass spectrum. This can be beneficial in some configurations where the ion transfer efficiency depends on m / z due to the variable ion cloud size when the ion storage 306 is implemented, for example, by a C-trap.

[0073] To illustrate, Figures 8A to 8B Shown with 7A to 7B The same mass spectra as shown in 500 and 700, except that Figures 8A to 8B In FIG, mass spectra 500 and 700 are divided into multiple ranges of m / z values. In particular, mass spectra 500 and 700 are divided into m / z ranges 802-1 to 802-4. Although in Figures 8A to 8B Four m / z ranges are depicted in , but it will be appreciated that mass spectra 500 and 700 may be divided into any number of m / z ranges.

[0074] The calibration management system 102 may use the 7A to 7BThe same technique described is used to determine the total ion count for the second ion population injected into the image current-based mass analyzer within each of the m / z ranges 802-1 to 802-4. For example, the calibration management system 102 can determine the total ion count for the first ion population injected into the electron multiplier-based mass analyzer across the m / z range 802-1, the peak ion count associated with peak 502-1, and the peak ion count associated with peak 702-1. Based on these ion counts, the calibration management system 102 can determine the total ion count for the second ion population injected into the image current-based mass analyzer within the m / z range 802-1. Similar techniques can be used to determine the total ion count for the second ion population within ranges 802-2 to 802-4. In some examples, the total ion count for the second ion population within each m / z range 802 can be summed to determine the overall total ion count for the second ion population across the entire m / z range. The total ion count for the second ion population across the entire m / z range can be used to set calibration parameters. Additionally or alternatively, based on the individual ion counts within the m / z range 802, the calibration management system 102 can determine different calibration parameters for each m / z range 802. Additionally or alternatively, the calibration management system 102 can set independent calibration parameters for multiple subsequent acquisition operations, each parameter tailored to a particular desired m / z range or bin (and thus determined by independently calibrating the total ion counts for each bin).

[0075] Figure 9 An exemplary computing device 900 is shown, which may be specifically configured to perform one or more of the operations, methods, and processes described herein. Any of the systems, computing devices, and / or other components described herein may be implemented by the computing device 900.

[0076] like Figure 9 As shown, computing device 900 may include a communication interface 902, a processor 904, a storage device 906, and an input / output ("I / O") module 908 communicatively connected to one another via a communication infrastructure 910. Figure 9 An exemplary computing device 900 is shown, but Figure 9 The components shown are not intended to be limiting. In other embodiments, additional or alternative components may be used. Figure 9 Components of computing device 900 are shown.

[0077] The communication interface 902 may be configured to communicate with one or more computing devices. Examples of the communication interface 902 include, but are not limited to, a wired network interface (such as a network interface card), a wireless network interface (such as a wireless network interface card), a modem, an audio / video connection, and any other suitable interface.

[0078] The processor 904 generally represents any type or form of processing unit capable of processing data and / or interpreting, executing, and / or directing one or more of the instructions, processes, and / or operations described herein. The processor 904 may perform operations by executing computer-executable instructions 912 (e.g., applications, software, code, and / or other executable data instances) stored in the storage device 906.

[0079] The storage device 906 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 devices. For example, the storage device 906 may include, but is not limited to, any combination of non-volatile media and / or volatile media as described herein. Electronic data, including the data described herein, may be temporarily and / or permanently stored in the storage device 906. For example, data representing computer-executable instructions 912 configured to direct the processor 904 to perform any of the operations described herein may be stored within the storage device 906. In some examples, the data may be arranged in one or more databases residing within the storage device 906.

[0080] The I / O module 908 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. The I / O module 908 may include any hardware, firmware, software, or combination thereof that supports input capabilities and output capabilities. For example, the I / O module 908 may include hardware and / or software for capturing user input, including but not limited to a keyboard or keypad, a touch screen component (e.g., a touch screen display), a receiver (e.g., an RF or infrared receiver), a motion sensor, and / or one or more input buttons.

[0081] I / O module 908 may include one or more devices for presenting output to the user, including but not limited to a graphics engine, a display (e.g., display screen), one or more output drivers (e.g., display driver), one or more audio speakers, and one or more audio drivers. In certain embodiments, I / O module 908 is configured to provide graphic data to the display to be presented to the user. Graphics data can represent one or more graphical user interfaces and / or any other graphic content as can serve a particular embodiment.

[0082] The advantages and features of the present disclosure are further described by the following statements:

[0083] 1. A system comprising: a memory storing instructions; and one or more processors communicatively coupled to the memory and configured to execute the instructions to perform a process comprising the steps of: determining a mass spectrum comprising one or more peaks based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, the one or more peaks representing intensities as a function of m / z for the first ion population across a range of mass-to-charge ratio (m / z) values; determining, based on the mass spectrum, a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values; determining, based on the total ion count and the peak ion count for the first ion population, a total ion count for a second ion population generated from the sample and injected into an image current-based mass analyzer for mass analysis; and setting calibration parameters for the image current-based mass analyzer based on the total ion count for the second ion population.

[0084] 2. A system according to statement 1, wherein the process further includes: determining an additional mass spectrum including one or more peaks based on the mass analysis performed on the second ion population by the image current-based mass analyzer, wherein the one or more peaks represent the intensity as a function of m / z of the second ion population across the range of m / z values; and determining additional peak ion counts associated with peaks at the specific m / z values ​​within the range of m / z values ​​based on the additional mass spectrum; wherein the determination of the total ion count of the second ion population is further based on the additional peak ion counts.

[0085] 3. The system of any of the preceding statements, wherein the mass spectrum further comprises one or more additional peaks representing intensity as a function of m / z of the first ion population across a range of additional mass-to-charge ratio (m / z) values, and

[0086] wherein the process further comprises: determining, based on the mass spectrum, additional total ion counts for the first ion population across the range of additional m / z values ​​and additional peak ion counts associated with additional peaks at specific m / z values ​​within the range of additional m / z values;

[0087] and determining additional total ion counts for the second ion population across the range of additional m / z values ​​based on the additional total ion counts and the additional peak ion counts.

[0088] 4. A system according to any of the preceding statements, wherein the process further comprises: determining an overall total ion count of the second ion population across both the range of m / z values ​​and the range of additional m / z values ​​based on the total ion count of the second ion population and the additional total ion count of the second ion population, wherein setting the calibration parameter is based on the overall total ion count.

[0089] 5. A system according to any of the preceding statements, wherein the process further comprises: directing an ion source to inject the first ion population into the electron multiplier-based mass analyzer as part of a pre-scan operation; and directing the ion source to inject the second ion population into the image current-based mass analyzer as part of a mass spectrometry acquisition operation performed after the pre-scan operation.

[0090] 6. The system according to any of the preceding statements, wherein the electron multiplier based mass analyser is implemented by a linear ion trap or a time-of-flight mass analyser.

[0091] 7. The system according to any of the preceding statements, wherein the image current based mass analyser is implemented by an orbital electrostatic trap mass analyser or a Fourier transform ion cyclotron resonance mass analyser.

[0092] 8. The system of any of the preceding statements, wherein the calibration parameters are configured to set a mapping between an oscillation frequency of the second ion population within the image current based mass analyser and the m / z value.

[0093] 9. The system according to any of the preceding statements, wherein the sample is generated using a liquid chromatography procedure.

[0094] 10. A system comprising: an electron multiplier-based mass analyzer configured to perform mass analysis on a first ion population generated from a sample; and a controller configured to determine, based on the mass analysis performed by the electron multiplier-based mass analyzer, a mass spectrum comprising one or more peaks, the one or more peaks representing a mass-to-charge ratio (m / z) across the first ion population.

[0095] a mass analyzer configured to perform mass analysis on a second ion population generated from the sample after the mass analysis performed by the electron multiplier based mass analyzer; wherein the controller is further configured to: determine, based on the mass analysis performed on the second ion population by the image current based mass analyzer, an additional mass spectrum including one or more peaks representing the intensity as a function of m / z of the second ion population across the range of m / z values; determine, based on the additional mass spectrum, an additional peak ion count associated with the peak at the specific m / z value within the range of m / z values; and determine, based on the total ion count, the peak ion count, and the additional peak ion count of the first ion population.

[0096] 11. The system of statement 10, wherein the controller is further configured to set calibration parameters for the image current based mass analyzer based on the total ion count of the second ion population.

[0097] 12. The system of any one of statements 10 to 11, wherein the calibration parameters are configured to set a mapping between an oscillation frequency of the second ion population within the image current based mass analyser and the m / z value.

[0098] 13. A system according to any one of statements 10 to 12, wherein the mass spectrum further comprises one or more additional peaks representing the intensity as a function of the m / z of the first ion population across a range of additional mass-to-charge ratio (m / z) values, and

[0099] wherein the controller is further configured to: determine, based on the mass spectrum, an additional total ion count of the first ion population across the range of additional m / z values ​​and an additional peak ion count associated with an additional peak at a specific m / z value located within the range of additional m / z values; and determine, based on the additional total ion count and the additional peak ion count, an additional total ion count of the second ion population across the range of additional m / z values.

[0100] 14. A system according to any one of statements 10 to 13, wherein the controller is further configured to: determine the overall total ion count of the second ion population across both the range of m / z values ​​and the range of additional m / z values ​​based on the total ion count of the second ion population and the additional total ion count of the second ion population, wherein the calibration parameter is set based on the overall total ion count.

[0101] 15. A system according to any one of statements 10 to 14, wherein the controller is further configured to: direct the ion source to inject the first ion population into the electron multiplier-based mass analyzer as part of a pre-scan operation; and direct the ion source to inject the second ion population into the image current-based mass analyzer as part of a mass spectrometry acquisition operation performed after the pre-scan operation.

[0102] 16. The system of any one of statements 10 to 15, wherein the electron multiplier-based mass analyzer is implemented by a linear ion trap or a time-of-flight mass analyzer.

[0103] 17. The system of any one of statements 10 to 16, wherein the image current based mass analyser is implemented by an orbital electrostatic trap mass analyser or a Fourier transform ion cyclotron resonance mass analyser.

[0104] 18. The system of any one of statements 10 to 17, wherein the sample is generated using a liquid chromatography procedure.

[0105] 19. A method comprising: determining a mass spectrum comprising one or more peaks based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, the one or more peaks representing intensities as a function of m / z of the first ion population across a range of mass-to-charge ratio (m / z) values; determining a total ion count of the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a specific m / z value within the range of m / z values ​​based on the mass spectrum; determining a total ion count of a second ion population generated from the sample and injected into a mirror current-based mass analyzer for mass analysis based on the total ion count and the peak ion count of the first ion population; and setting calibration parameters for the mirror current-based mass analyzer based on the total ion count of the second ion population.

[0106] 20. The method according to statement 19 further includes: determining an additional mass spectrum including one or more peaks based on the mass analysis performed on the second ion population by the mirror current-based mass analyzer, the one or more peaks representing the intensity as a function of m / z of the second ion population across the range of m / z values; and determining additional peak ion counts associated with the peaks at the specific m / z values ​​within the range of m / z values ​​based on the additional mass spectrum; wherein the determination of the total ion count of the second ion population is further based on the additional peak ion counts.

[0107] In the foregoing description, various exemplary embodiments have been described with reference to the accompanying drawings. However, it will be apparent that various modifications and alterations may be made thereto, and additional embodiments may be implemented, without departing from the scope of the present invention as set forth in the appended claims. For example, certain features of one embodiment described herein may be combined with or substituted for features of another embodiment described herein. Accordingly, the description and drawings are to be regarded as illustrative rather than restrictive.

Claims

1. A system, comprising: a memory storing instructions; and one or more processors communicatively coupled to the memory and configured to execute the instructions to perform a process comprising: determining, based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, a mass spectrum comprising one or more peaks representing intensity as a function of mass-to-charge ratio (m / z) of the first ion population across a range of m / z values; determining, based on the mass spectrum, a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values; determining a total ion count of a second ion population generated from the sample and injected into an image current-based mass analyzer for mass analysis based on the total ion count and the peak ion count of the first ion population; as well as Calibration parameters for the image current based mass analyzer are set based on the total ion count of the second ion population.

2. The system of claim 1 , wherein the process further comprises: determining, based on the mass analysis performed by the image current based mass analyzer on the second ion population, an additional mass spectrum comprising one or more peaks representing intensity as a function of m / z for the second ion population across the range of m / z values; as well as determining, based on the additional mass spectra, additional peak ion counts associated with a peak at the particular m / z value within the range of m / z values; Wherein the determining of the total ion count of the second ion population is further based on the additional peak ion count.

3. The system of claim 1 , wherein the mass spectrum further comprises one or more additional peaks representing intensity as a function of m / z of the first ion population across a range of additional mass-to-charge ratio (m / z) values, and wherein the process further comprises: determining, based on the mass spectrum, additional total ion counts for the first ion population across the range of additional m / z values ​​and additional peak ion counts associated with additional peaks at specific m / z values ​​within the range of additional m / z values; as well as Additional total ion counts for the second ion population across the range of additional m / z values ​​are determined based on the additional total ion counts and the additional peak ion counts.

4. The system of claim 3, wherein the process further comprises: An overall total ion count for the second ion population across both the range of m / z values ​​and the range of additional m / z values ​​is determined based on the total ion count for the second ion population and the additional total ion count for the second ion population, wherein setting the calibration parameter is based on the overall total ion count.

5. The system of claim 1 , wherein the process further comprises: directing an ion source to inject the first ion population into the electron multiplier-based mass analyzer as part of a pre-scan operation; as well as The ion source is directed to population-inject the second ion into the image current-based mass analyzer as part of a mass spectrometry acquisition operation performed after the pre-scan operation.

6. The system of claim 1, wherein the electron multiplier-based mass analyzer is implemented by a linear ion trap or a time-of-flight mass analyzer.

7. The system of claim 1, wherein the image current based mass analyzer is implemented by an orbital electrostatic trap mass analyzer or a Fourier transform ion cyclotron resonance mass analyzer.

8. The system of claim 1, wherein the calibration parameters are configured to set a mapping between an oscillation frequency of the second ion population within the image current based mass analyzer and the m / z value.

9. The system of claim 1, wherein the sample is generated using a liquid chromatography procedure.

10. A system comprising: an electron multiplier-based mass analyzer configured to perform mass analysis on a first ion population generated from the sample; A controller configured to: determining, based on the mass analysis performed by the electron multiplier-based mass analyzer, a mass spectrum comprising one or more peaks representing intensity as a function of mass-to-charge ratio (m / z) of the first ion population across a range of m / z values; as well as determining, based on the mass spectrum, a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values; and an image current-based mass analyzer configured to perform mass analysis on a second ion population generated from the sample after the mass analysis performed by the electron multiplier-based mass analyzer; The controller is further configured to: determining, based on the mass analysis performed by the image current based mass analyzer on the second ion population, an additional mass spectrum comprising one or more peaks representing intensity as a function of m / z for the second ion population across the range of m / z values; determining, based on the additional mass spectra, additional peak ion counts associated with a peak at the particular m / z value within the range of m / z values; as well as A total ion count for the second ion population is determined based on the total ion count, the peak ion count, and the additional peak ion count for the first ion population. 11 . The system of claim 10 , wherein the controller is further configured to set calibration parameters for the image current based mass analyzer based on the total ion count of the second ion population.

12. The system of claim 11, wherein the calibration parameters are configured to set a mapping between an oscillation frequency of the second ion population within the image current based mass analyzer and the m / z value.

13. The system of claim 10 , wherein the mass spectrum further comprises one or more additional peaks representing intensity as a function of m / z of the first ion population across a range of additional mass-to-charge ratio (m / z) values, and wherein the controller is further configured to: determining, based on the mass spectrum, additional total ion counts for the first ion population across the range of additional m / z values ​​and additional peak ion counts associated with additional peaks at specific m / z values ​​within the range of additional m / z values; and Additional total ion counts for the second ion population across the range of additional m / z values ​​are determined based on the additional total ion counts and the additional peak ion counts.

14. The system of claim 13 , wherein the controller is further configured to determine an overall total ion count for the second ion population across both the range of m / z values ​​and the range of additional m / z values ​​based on the total ion count for the second ion population and the additional total ion count for the second ion population, wherein setting the calibration parameter is based on the overall total ion count.

15. The system of claim 10, wherein the controller is further configured to: directing an ion source to inject the first ion population into the electron multiplier-based mass analyzer as part of a pre-scan operation; and The ion source is directed to population-inject the second ion into the image current-based mass analyzer as part of a mass spectrometry acquisition operation performed after the pre-scan operation.

16. The system of claim 10, wherein the electron multiplier-based mass analyzer is implemented by a linear ion trap or a time-of-flight mass analyzer.

17. The system of claim 10, wherein the image current based mass analyzer is implemented by an orbital electrostatic trap mass analyzer or a Fourier transform ion cyclotron resonance mass analyzer.

18. The system of claim 10, wherein the sample is generated using a liquid chromatography procedure.

19. A method comprising: determining, based on mass analysis performed by an electron multiplier-based mass analyzer on a first ion population generated from a sample, a mass spectrum comprising one or more peaks representing intensity as a function of mass-to-charge ratio (m / z) of the first ion population across a range of m / z values; determining, based on the mass spectrum, a total ion count for the first ion population across the range of m / z values ​​and a peak ion count associated with a peak at a particular m / z value within the range of m / z values; determining a total ion count of a second ion population generated from the sample and injected into an image current-based mass analyzer for mass analysis based on the total ion count and the peak ion count of the first ion population; as well as Calibration parameters for the image current based mass analyzer are set based on the total ion count of the second ion population.

20. The method according to claim 19, further comprising: determining, based on the mass analysis performed by the image current based mass analyzer on the second ion population, an additional mass spectrum comprising one or more peaks representing intensity as a function of m / z for the second ion population across the range of m / z values; as well as determining, based on the additional mass spectra, additional peak ion counts associated with a peak at the particular m / z value within the range of m / z values; Wherein the determining of the total ion count of the second ion population is further based on the additional peak ion count.

Images